Bi-level positive airway pressure (BiPAP) ventilation in an infant with central hypoventilation syndrome

OBJECTIVES: To determine the effects of long-term cigarette smoking on the levels of plasma testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in male adult rats and to examine morphological and histological changes in the testes. MATERIALS AND METHODS: Cigarette smoke was generated by a smoking-machine and 12 rats were exposed to cigarette smoke diluted with 90% air for 60 days (2 h/day). Twelve rats were exposed to room air only under similar conditions as controls. The concentrations of plasma testosterone, LH and FSH were measured before and after exposure using a radio-immunoassay and the testes were examined histologically. RESULTS: In rats exposed to smoke, the mean plasma testosterone level decreased significantly but there were no significant changes in testosterone in the control rats. The mean plasma LH and FSH levels of the two groups did not change significantly after exposure. In rats exposed to smoke, histological examination of the testes showed fewer Leydig cells and degeneration of the remaining cells. CONCLUSION: These results indicate that the decrease in plasma testosterone levels induced by exposure to smoke was not associated with changes in plasma gonadotrophin levels. The decrease in testosterone levels may be related to the toxic effects of smoke on Leydig cells.     

Effects of external cadmium ions on excitation-contraction coupling in rat soleus fibres

Administration of 4 mg of the antisteroid RU486 over 8 consecutive days to adult male rats dissociated in vivo and in vitro gonadotrophin secretion, increasing FSH and decreasing LH secretion. In subsequent experiments we evaluated the involvement of testicular or adrenal secretory products, as well as hypothalamic LHRH, in the effects of 4 consecutive days of RU486 treatment on the secretion of gonadotrophins. The first day of RU486 injection was designated day 1, subsequent days being numbered consecutively. Groups of rats injected with oil (0.2 ml) or RU486 (4 mg) were: (i) injected s.c. from day 1 to day 4 with the antiandrogen flutamide (10 mg/kg); (ii) bilateral orchidectomized (ORCH) on day 1; and (iii) bilateral adrenalectomized (ADX) on day 1. Controls were given flutamide vehicle or were sham operated. To ascertain whether the secretion of LHRH is involved in the effects of RU486 on gonadotrophin secretion, we measured the LHRH secretion into the pituitary stalk blood vessels at 1100 h on day 5 in oil- or RU486-treated rats. Additional oil- and RU486-treated rats were injected i.p. with 100 ng LHRH at 1000 h on day 5, or s.c. with 1 mg LHRH antagonist (LHRH-ANT) at 1000 h on days 2 and 4. Controls were given saline. All animals were decapitated at 1100 h on day 5, trunk blood collected and serum stored frozen until FSH, LH and testosterone assays.%While ADX had no effect on FSH and LH secretion in either oil- or RU486-treated rats, the removal of androgen negative feedback with flutamide treatment or by ORCH substantially increased serum levels of FSH and LH in both oil- and RU486-treated rats, and thus annulled the effects of RU486. No differences in pituitary stalk plasma LHRH concentrations were found between oil- and RU486-treated rats. Injection of LHRH increased serum FSH and LH concentrations in oil-treated rats but only, and to a lesser extent, LH concentrations in RU486-treated rats. Treatment with LHRH-ANT decreased serum concentrations of FSH and LH in both oil- and RU486-treated rats. These results suggest that RU486 inhibited LHRH-stimulated LH secretion at the pituitary level, and that FSH secretion increased in response to a reduction in the negative feedback of androgen.     

Seasonal and circadian changes in the episodic release of follicle-stimulating hormone, luteinizing hormone and testosterone in rams exposed to artificial photoperiods

Six rams of an ancient breed of domesticated sheep (SOAY) were subjected to an artificial light régime of alternating periods of long days (16 h light: 8 h darkness) and short days (8 h light: 16 h darkness) which induced seasonal development and regression of the testes during a period of 36 weeks. Over 2000 blood samples were taken, and the changes in plasma levels of FSH, LH and testosterone were related to the cycle of testicular activity. During long days plasma levels of gonadotrophins became very low and the testes regressed to about 20% of their maximum size; there was a corresponding reduction in plasma testosterone levels. When the rams were returned to short days reproductive development was again stimulated after 2-3 weeks with a progressive increase in plasma FSH and LH levels and consequent hypertrophy of the testes. It took about 16 weeks of short days for testicular activity to become maximal. Blood samples collected at hourly intervals for 24 h on ten occasions during the study revealed transitory peaks in plasma FSH and LH levels indicative of episodic release. Changes in gonadotrophin secretion were modulated primarily by alterations in the frequency of episodic releas; less than 1 spike per 24 h during long days increased to a maximum of 10 spikes/24 h under short daylengths. The peaks of FSH release were of smaller amplitude than those of LH, although during periods of frequent episodic release basal levels of fsh were increased to a greater extent than those of LH. A circadian rhythm was observed in the plasma levels of FSH, LH and testosterone, which was related to increased gonadotrophin release during the dark phase of the 24 h cycle; changes in blood haematocrit were also observed. The circadian changes appeared to be correlated with the activity cycle of the animals which in turn was dictated by daylight. A possible interrelationship between the circadian cycle and the seasonal cycle is discussed.     

Differences of the effects of testosterone propionate on the production of LH and FSH

The effects of testosterone propionate (1 mg/day) on the synthesis and circulating levels of FSH and LH were studied in normal adult male rats. The pituitary and serum gonadotrophins were measured by double antibody radioimmunoassay. The de novo synthesis of gonadotrophins was assessed by the rate of in vitro incorporation of [3H]leucine into the immunoprecipitable FSH and LH. After 4 days of treatment with testosterone propionate the circulating LH levels dropped significantly, while FSH remained unchanged. Pituitary LH content and concentration declined significantly after 1 day, and incorporation of [3H]leucine into the immunoprecipitable LH became undetectable 4 days after initiation of treatment. Pituitary FSH content and concentration showed a significant increase after the 4th day of treatment. A slight tendency towards increased incorporation of [3H]leucine into FSH was observed throughout the treatment period, although it was statistically not significant. The data provide direct evidence for a differential effect of TP on FSH and LH production by the pituitary and show that the decrease in the pituitary and plasma levels of LH in testosterone treated rats is due to the decrease in LH synthesis.     

Age-dependent effects of hippocampal muscarinic receptor blockade on memory-based learning in the developing rat

In the male rat, testosterone has been shown to regulate gonadotrophin synthesis and secretion under experimental conditions such as castration or gonadotrophin-releasing hormone (GnRH) antagonist with or without testosterone. The present study aims at clarifying the effects of non-steroidal antiandrogens, Casodex and flutamide, and ethane dimethane sulphonate (EDS) on the regulation of gonadotropin synthesis and secretion. To enable a direct comparison within this study to expected effects of testosterone, a GnRH antagonist-treated group and a castrated group were included. The gene expression of the subunits was correlated with changes in the pituitary and plasma content of immunoreactive luteinizing hormone (LH) and follicle-stimulating hormone (FSH), free subunits and pituitary content of in vitro bioactive LH and FSH. Groups of ten male rats each received the following treatments for 7 days: (1) vehicle; (2) castration; (3) EDS (75 mg/kg); (4) GnRH antagonist (Cetrorelix 250 micrograms/kg/day), (5) Casodex (20 mg/kg/day) or (6) flutamide (20 mg/kg/day). The effectiveness of testosterone deprivation was demonstrated by the reduction of weight in androgen-dependent organs such as epididymides and seminal vesicles in the treated groups. Treatment with flutamide, EDS or castration significantly increased (p < 0.05) serum levels of LH, FSH and alpha-subunit, whereas serum gonadotrophin levels were decreased in the GnRH antagonist-treated group. alpha-Subunit mRNA levels were elevated in the castrated, EDS and flutamide group and LH-beta mRNA levels were increased in the castrated and EDS group. FSH-beta mRNA levels were increased in the castrated group and decreased in the GnRH antagonist group, but remained unchanged in the flutamide and EDS group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Follicle-stimulating hormone in azoospermia in prediction of spermatogenic patterns

Follicle-stimulating hormone (FSH) is considered to be the most important plasma hormone correlated with spermatogenesis. Elevated FSH plasma levels were shown to be associated with complete damage to testicular seminiferous tubule germinal epithelium. Recently, there have been conflicting reports with regard to the value of FSH plasma levels in predicting seminiferous tubule histology in the azoospermic patient and hence, as a guide for therapy in assisted reproduction using testicular sperm retrieval. The aim of this study was to evaluate whether FSH plasma levels can predict spermatogenic pattern in the testes of the azoospermic infertile patient. 69 infertile men with non-obstructive azoospermia and 18 with very severe oligospermia were studied. In all, plasma levels of testosterone, free testosterone, prolactin, luteinizing hormone and follicle-stimulating hormone were measured by enzyme immunoassay. In the azoospermic patients the seminiferous tubule spermatogenic pattern was determined in testicular aspirates obtained by multiple fine needle aspiration and categorized according to the most mature spermatogenic cell type in the aspirates: Sertoli cells only, spermatogenic maturation arrest or full spermatogenesis. There were no significant differences in plasma levels of any hormone measured except in very severely oligospermic and azoospermic patients. Both normal and elevated levels were detected in all, regardless of seminiferous tubule cytological pattern or plasma FSH in azoospermic patients. It is concluded that plasma levels of FSH can not be used as a predictive parameter, neither for the presence of spermatozoa nor for any other seminiferous tubule cytological pattern in azoospermic infertile men. They cannot serve as guides for selection of azoospermic men for trials of testicular sperm retrieval in assisted reproduction.     

Heterotopic transplantation as a model to study the regulation of spermatogenesis; some histomorphological considerations about sperm decline in man

A novel animal model (syngeneic neonatal testicular graft transplanted under the skin of the outer ear in adult inbred Fischer rats that had been castrated, hypophysectomised, and/or subjected to hormonal replacement therapy) was developed to study regulation of spermatogenesis and Sertoli cell number. Given that Sertoli cell number and testicular size are important in determining spermatozoan production rates, this model was first used to study Sertoli cell proliferation, testicular size, and establishment of germ cells. The specific objectives were to determine the developmental pattern of Sertoli cell numbers in transplanted testes and the effect of number of testes transplanted, sex of hosts, pituitary hormonal removal, and replacement on Sertoli cell number, hormonal status of the host, and establishment of germ cells. A few tubules had complete spermatogenesis at 90 days posttransplantation, indicating that Sertoli cells in some of these tubules were functional. Leydig cell structure appeared to be normal, but the density of these interstitial cells was greater than that in testes of intact rats. Although the weight of the seminal vesicles and prostate were maintained in the castrated host with transplants, both serum FSH and LH concentrations were higher than intact control rats. Leukocytic infiltration of testes was not observed in intact rats or in rats receiving neonatal testes. Although transplanted testes showed a delay in reaching the plateau value for Sertoli cell number per testis and although the value reached was lower than in intact testes, the developmental pattern of Sertoli cell proliferation (early division of cells followed by stabilized number of cells) in transplanted testes was similar to that in intact rats. Hypophysectomy reduced the growth of testicular grafts, and hormonal replacement via retransplantation to pituitary intact hosts enhances Sertoli cell proliferation and testicular growth. When two on four testes were transplanted into castrated males or ovariectomized female hosts for 65 days, there was no difference in the graft weights or Sertoli cell numbers between sexes of hosts. Four transplanted testes per rat produced more total testicular parenchyma and a greater number of Sertoli cells per testis than did two testes regardless of sex of the host. Transplantation of six or eight testes produced more total Sertoli cells/host than that found in testes of intact rats. Using hormonal therapy in hypophysectomized hosts, the testicular parenchymal weight was greater for pituitary-intact hosts and FSH-LH combination than the control media. There was no statistically significant difference among the media control, LH, FSH, and GH. This testicular transplant model has shown that the period of Sertoli cell proliferation can be delayed by hypophysectomy, that Sertoli cell number can be influenced by endogenous and exogenous hormones, and that a major component in regulation of testicular size is at the level of the testis. Hence, this model should facilitate study of experimental endocrine manipulation control and potential experimental intervention to increase Sertoli cell number, testicular size, and spermatogenesis. Regarding human sperm count decline in recent years, there appears to be no significant decline in Sertoli cell number or spermatogenic potential in a group of North American men. However, there was a significant decline in volume/man of Leydig cells and volume/man of Leydig cell cytoplasm.     

Changes in the pituitary-testicular system with age

In order to provide a comprehensive account of pituitary-testicular function in man, 466 subjects, ranging in age from 2 to 101 years, were studied to examine blood levels of the pituitary gonadotrophins (LH and FSH), the sex steroids testosterone and oestradiol, the binding capacity of the sex hormone binding globulin (SHBG), the free testosterone and oestradiol fractions, and the transfer constant for the peripheral conversion of testosterone to oestradiol. The results were compared with clinical indices of testicular size, sexual function and secondary sex hair distribution. Serum LH and FSH were low before puberty, increased in pubertal adolescents to levels somewhat above those of adults and subsequently increased progressively over the age of 40 years. Testosterone levels fell slowly after the age of 40, while there was a slight rise in plasma oestradiol with increasing age. FSH and testosterone showed small seasonal variations in young adult men, the lowest values being seen in winter. SHBG binding capacity was high in two prepubertal boys, fell in adult men, but increased in old age. Free testosterone and oestradiol levels fell in old age. The metabolic clearance rates (MCR) of testosterone and oestradiol also fell in old age, while the conversion of testosterone to oestradiol was increased. Many correlations were observed between various hormonal and clincial measurements. The evidence is consistent with a primary decrease in testicular function over the age of 40 years.     

Age-related decreased Leydig cell testosterone production in the brown Norway rat

Previous studies have demonstrated that Leydig cell testosterone production diminishes with age in Brown Norway rats. The objective of the studies presented herein was to test the following possible explanations for age-related decline in steroidogenesis: (1) decline in Leydig cell number; (2) understimulation by luteinizing hormone (LH); (3) reduced ability of individual Leydig cells to produce testosterone; and (4) influence of loss of germ cells. Leydig cells isolated from the testes of young and aged rats by centrifugal elutriation and Percoll density gradient centrifugation were examined for their ability to produce testosterone when stimulated maximally with LH or with dibutyryl cyclic AMP (dbcAMP). Leydig cell number and volume were examined in situ using stereological methods. Serum LH levels were measured using a highly sensitive immunofluorometric assay. Average Leydig cell volume decreased with age, and consistent with this observation, individual Leydig cells isolated from aging rats produced significantly less testosterone than those from young rats whether the cells were cultured in vitro with maximally stimulating LH or with dbcAMP. The age-associated diminished testosterone production could not be explained by changes in Leydig cell number, serum LH levels, Leydig cell responsiveness to LH, or testicular germ cell content. These results, taken together, suggest that the reduced testosterone production seen in aged rats is related to defects in the steroidogenic pathway beyond the LH receptor-cAMP cascade. The nature of the initial age-related changes that cause reduced steroidogenesis is not known, and therefore it is not known whether such changes are intrinsic or extrinsic to the Leydig cells.     

Effects of tylosin on the pituitary-gonadal axis in male rats

Former investigations in rats showed a decrease of thyroid hormone concentrations after treatment with the antibiotic and growth promoter tylosin (Sch?fer 1984). In the present study, the effects of tylosin on the pituitary-gonadal axis in adult rats were studied. The substance was administered in two concentrations to rats (0.1 and 5.0 mg tylosin/kg feed) for three different periods: 15, 29 and 65 days. At the end of each period the organ weights were determined and the hormone levels in serum and pituitary gland were measured by radioimmunoassay. After 15 days reduced levels of LH (luteinizing hormone) and FSH (follicle stimulating hormone) in the pituitary gland and LH in serum were found. Moreover, the weight of seminal vesicles was decreased and the weight of pituitary increased. After 29 days an equilibrium between effects of tylosin and endocrine contraregulation seemed to be achieved. The prolonged tylosin administration (65 days) depressed testosterone concentration and increased hypophyseal LH stores. The testing of the pituitary-testicular axis with acute LHRH (luteinizing hormone-releasing hormone) stimulation caused a reduced increase of LH in animals treated with 0.1 mg tylosin. In contrast, the LH responsiveness to LHRH in animals treated with 5.0 mg tylosin was unchanged, while the testosterone response to released LH was reduced. These findings demonstrate that tylosin acts on the pituitary as well as on peripheral functions of the pituitary-gonadal-axis and that its effects depends on the time interval of tylosin administration.     

Effect of inorganic fluorine compounds on the functional state of the pituitary-testis system

The radioimmunological method was applied to the study of blood testosterone, LH, and FSH content in 41 men suffering from fluorosis, aged from 33 to 45 years. Nineteen men who had no contact with fluorine compounds served as control. In comparison with healthy individuals testosterone content proved to be decreased and FSH content elevated in patients with fluorosis. Blood LH content was increased only in those patients with fluorosis who had long contact with fluorine compounds (over 15 years). The changes in the blood hormone concentration were connected with disturbances of the hormonal, and, possibly, of the germenative function of the testes. The hypophysis proved to suffer less, and the changes of its function were apparently secondary in character.     

Classification of several types of maturational arrest of spermatogonia according to Sertoli cell morphology: an approach to aetiology

Bilateral testicular biopsies and clinical histories from 34 adult men with maturational arrest of spermatogonia were examined. According to the morphology of Sertoli cell nuclei, five testicular types of spermatogonial maturational arrest were established. In type I lesion, Sertoli cells resembled the immature Sertoli cells of infant testes. These cells had a round, regularly outlined, dark nucleus with a small nucleolus. The seminiferous tubules showed no apparent lumen and a poorly developed lamina propria lacking in elastic fibres. This lesion was found in patients exhibiting a eunuchoid phenotype, with small tests and low serum levels of gonadotrophins and testosterone (hypogonadotrophic hypogonadism). Type II lesion showed morphologically normal, mature, adult Sertoli cells which had a pale, irregularly outlined nucleus, many often triangle-shaped, with a large, centrally located nucleolus. The seminiferous tubules were reduced in diameter and showed a few spermatocytes and spermatids. This lesion was found in patients with varicocoele, epididymitis, testicular trauma or idiopathic infertility. Serum FSH levels were normal or increased while LH and testosterone levels were normal. In type III lesion, Sertoli cells resembled the involuting Sertoli cells found in the testes of aging men, and displayed very infolded nuclei, with abundant dense chromatin patches and a large nucleolus. The seminiferous tubules showed a slightly dilated lumen and a normal tubular wall. The most relevant clinical findings in patients with this lesion were alcoholism, varicocoele, falciform cell anaemia, epididymitis and germ cell tumour. Serum follicle stimulating hormone (FSH) levels were normal or increased while luteinizing hormone (LH) and testosterone levels were normal. Type IV lesion Sertoli cells presented with a de-differentiated appearance. These cells had a small, round euchromatic nucleus with a small nucleolus and vacuolated cytoplasm. The seminiferous tubules were devoid of lumen or ectatic, and the tubular wall was thick and contained abundant elastic fibres. This lesion was characteristic of patients who underwent hormonal treatment because of prostatic carcinoma or sex change. Type V lesion showed abnormally differentiated, probably dysgenetic, Sertoli cells which had a round to ovoid regularly outlined nucleus, with small heterochromatin granules, and the number of these cells was increased. The seminiferous tubules had a central lumen, or were ectatic with vacuolated Sertoli cells, and the amount of elastic fibres was decreased. The most relevant clinical finding in patients with this lesion was orchidopexy. Serum FSH and LH levels were normal or slightly increased. These findings indicate that spermatogonial maturational arrest is associated with a characteristic Sertoli cell morphology that can be easily identified. This morphology may shed light on the aetiology of the disorder, and be useful for establishing the prognosis and bases for treatment in subfertile patients.     

Photoperiodic control of gonadotrophin secretion in the ram: a detailed study of the temporal changes in plasma levels of follicle-stimulating hormone, luteinizing hormone and testosterone following an abrupt switch from long to short days

Six adult Soay rams were housed under artificial lighting conditions of long days (16 h light:8 h darkness) for 4 months and this caused the animals to lapse into a state of reproductive quiescence with low levels of gonadotrophins in the circulation and regressed testes secreting very low amounts of testosterone. The photoperiod was changed abruptly to short days (8 h light:16 h darkness) to induce a resurgence of sexual activity, and a detailed study was made of the pituitary and testicular responses over the first 100 days. Plasma levels of LH and FSH first began to increase between days 6 and 12 of short days, and rose progressively until days 33-54 before declining again. Testicular growth of the rams began on days 19-26 and continued for most of the remaining period of study. Plasma testosterone levels rose in parallel with the growth of the testes, and were greatly increased by day 100 when gonadotrophin levels were reduced. At most stages there were short-term fluctuations in the plasma levels of FSH, LH and testosterone indicative of episodic secretion. Peaks in plasma levels of LH were especially conspicuous and from the changes in frequency and amplitude of these peaks it was possible to predict the way in which photoperiod influenced gonadotrophin secretion by its effect on hypothalamic LH-RH secretion. A slight 24 h rhythm in the plasma levels of all three hormones was observed, and the significance of this in relation to the photoperiodic response is discussed.     

Endocrine therapy of transsexualism and potential complications of long-term treatment

Physiological principles of the interrelationship of sex hormones and their regulation are the foundation of understanding appropriate treatment of the transsexual patient. While both genetic males and females have estrogens and androgens, the quantitative sex hormone production is genetically predetermined by sex hormone production both in the gonads and via peripheral conversion of hormone precursors to sex steroids. Sex hormones exert a negative feedback on the hypothalamus and pituitary gland whereby gonadotropin-releasing hormone (GnRH), pituitary luteinizing hormone (LH), and follicle-stimulating hormone (FSH) are regulated or suppressed by the endogenous levels of these hormones. Sex hormonal therapy induces attenuated GnRH stimulation of LH and FSH causing a reduction of serum sex hormone levels. It is clear that estrogen as well as androgen therapy have a dual role: (i) induction of feminization or virilization and (ii) suppression of the hypothalamic-pituitary-gonadal axis leading to a reduction of endogenous estradiol or testosterone secretion. Cross-sex hormonal treatment may have substantial medical side effects. The smallest dosage of hormonal therapy compatible with the above clinical aims should be used.     

Serum inhibin B in healthy pubertal and adolescent boys: relation to age, stage of puberty, and follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol levels

Inhibin B levels were measured in serum from 400 healthy Danish prepubertal, pubertal, and adolescent males, aged 6-20 yr, in a cross-sectional study using a recently developed immunoassay that is specific for inhibin B, the physiologically important inhibin form in men. In addition, serum levels of FSH, LH, testosterone, and estradiol levels were measured. Serum levels of inhibin B, FSH, LH, testosterone, and estradiol all increased significantly between stages I and II of puberty. From stage II of puberty the inhibin B level was relatively constant, whereas the FSH level continued to increase between stages II and III. From stage III of puberty the FSH level was also relatively constant, although there was a nonsignificant trend of slightly decreased FSH levels at pubertal stage V compared to stage IV. The levels of serum LH, testosterone, and estradiol increased progressively throughout puberty. In prepubertal boys younger than 9 yr, there were no correlation between inhibin B and the other three hormones. In prepubertal boys older than 9 yr, a significant positive correlation was observed between inhibin B and FSH, LH, and testosterone. However, at this pubertal stage, each hormone correlated strongly with age, and when the effect of age was taken into account, only the partial correlation between inhibin B and LH/testosterone remained statistically significant. At stage II of puberty, the positive partial correlation between inhibin B and LH/testosterone was still present. At stage III of puberty, an negative partial correlation between inhibin B and FSH, LH, and estradiol was present, whereas no correlation between inhibin B and testosterone could be observed from stage III onward. The negative correlation between inhibin B and FSH persisted from stage III of puberty onward, whereas the correlation between inhibin B and LH and between inhibin B and estradiol was nonsignificant at stages IV and V of puberty. In conclusion, in boys, serum inhibin B levels increase early in puberty; by pubertal stage II the adult level of inhibin B has been reached. The correlation of inhibin B to FSH, LH, and testosterone changes during pubertal development. Early puberty is characterized by a positive correlation between inhibin B and LH/testosterone, but no correlation to FSH. Late puberty (from stage III) is characterized by a negative correlation between inhibin B and FSH (which is maintained in adult men), a diminishing negative correlation between inhibin B and LH, and no correlation between inhibin B and testosterone, suggesting that developmental and maturational processes in the hypothalamic-pituitary-gonadal axis take place, leading to the establishment of the closed loop feedback regulation system operating in adult men. The positive correlation between inhibin B and LH/ testosterone at the time when serum inhibin B levels rise early in puberty suggests that Leydig cell factors may play an important role in the maturation and stimulation of Sertoli cells in the beginning of pubertal development.     

Early supported hospital discharge following acute stroke: pilot study results

The effect of high-dose cranial- and craniospinal irradiation and chemotherapy on the gonadotropin-sex steroid axis was studied during different stages of puberty by measuring pulsatile secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. The patients were thirteen boys who had been treated for malignant brain tumor residing well away from the hypothalamo-pituitary region. The median time to follow-up was 9 (1-16) years. The onset of puberty was early in the patients, median 10.5 years, compared to the average age for Swedish boys, which is at median 12.4 years. There was, before puberty, no significant difference in LH and FSH secretion between patients and a control group of normal boys. In early, mid- and late stages of puberty, however, LH and FSH secretion was increased in the patients overall, whereas testosterone secretion was maintained within the normal range in spite of signs of gonadotoxocity with small testicular volumes. These results indicate that the vulnerable parts of the gonadotropin releasing hormone (GnRH)-gonadotropin (LH, FSH)-gonadal axis are the regulatory system that determines the timing of pubertal induction and the gonads. The GnRH-LH, FSH-releasing neurons appear relatively resistant to cranial irradiation as they are able to respond with supranormal LH and FSH levels for long periods of time after treatment.     

Probing the contribution of internal cavities to the volume change of protein unfolding under pressure

BACKGROUND: Testicular dysfunction with elevated follicle-stimulating hormone (FSH) levels (indicating oligospermia and/or azoospermia) is a major late sequelae after treatment for Hodgkin's disease (HD) with high cumulative doses of procarbazine, cyclophosphamide, or chlorambucil. Etoposide is a newer antineoplastic agent that is effective in the treatment of HD. However, little is known regarding its testicular toxicity, especially in the pediatric age group. METHODS: The authors evaluated testicular function in 46 young adults in first continuous complete remission after stage-dependent treatment for HD with the vincristine, etoposide, prednisone, and doxorubicin (OEPA) or OEPA/cyclophosphamide, vincristine, procarbazine, and prednisone [COPP] chemotherapy regimens and involved field irradiation, excluding patients with ilioinguinal radiotherapy. Pubertal development was documented and a standardized intravenous gonadotropin-releasing hormone test was performed measuring testosterone and basal and stimulated levels of FSH and luteinizing hormone (LH). RESULTS: Testicular volumes, Tanner stages of pubic hair, and genital development were found to be appropriate or slightly delayed for the patients' chronologic age. All 27 patients had normal basal levels of FSH and LH after treatment of Ann Arbor Stage I-IIA HD with 2 courses of OEPA. Stimulated FSH and LH levels were found to be elevated only in rare patients, thus indicating normal endocrine function and spermatogenesis. However, basal and stimulated FSH levels were outside the +2 standard deviation range in 37.5% and 83.3% of patients receiving 2 cycles of OEPA and 2 cycles of COPP chemotherapy, and in 36.4% and 66.7% of patients receiving 2 cycles of OEPA and 4 cycles of COPP chemotherapy, demonstrating a high risk of oligospermia or azoospermia with these regimens. Basal LH levels essentially were normal, whereas stimulated LH levels frequently were elevated. CONCLUSIONS: Testicular function was found to be normal in patients with Stage I-IIA HD when etoposide was used in combination with vincristine, prednisone, and doxorubicin (2 cycles of OEPA). Additional chemotherapy with cyclophosphamide and procarbazine (2 cycles of OEPA and 2 or 4 cycles of COPP) negatively affected spermatogenesis and possibly Leydig cell function in a considerable number of patients. This major gonadotoxic effect most likely is due to procarbazine, although an additional effect of etoposide and cyclophosphamide cannot be excluded.     

Effect of infarct artery patency on prognosis after acute myocardial infarction. The Survival and Ventricular Enlargement Investigators

In this study, adult male rats were injected intraperitoneally with a single dose of serotonin (5-hydroxytryptamine, 5HT; 10 mg kg-1 bodyweight) for 2 h or 18 h, or daily with graded doses of 5HT (0.1-10 mg kg-1) for four days before being killed. Serum and testicular interstitial fluid (IF) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and immunoreactive-inhibin were measured by radioimmunoassay, and one testis was removed for histological examination. At 2 h after a single injection, 5HT caused a significant inhibition of serum concentrations of LH and inhibin, recovered IF volume and intratesticular testosterone concentrations; testis weight and serum concentrations of testosterone and FSH were unaffected. At 18 h after injection, all parameters had returned to normal, with the exception of intratesticular testosterone concentration which remained lower than normal. The lowest 5HT dose (0.1 mg kg-1) had no effect on any parameter following four daily injections. At a dose of 1.0 mg kg-1 5HT, there was a four-fold increase in the concentration of serum LH, but testis weight, recovered IF volume, testosterone and inhibin concentrations and serum concentrations of FSH were not significantly affected. At the highest dose of 5HT (10 mg kg-1) after four daily injections, testis weight decreased, and IF volume increased nearly three-fold. Testis concentrations of inhibin and serum testosterone were reduced, whereas serum concentrations of both LH and FSH were elevated; intratesticular testosterone concentrations did not differ from controls. Only at the highest dose of 5HT was disruption to the seminiferous epithelium observed, with focal damage ranging in severity from increased degeneration of spermatogenic cell profiles, to complete loss of the germinal epithelium; however, many tubule profiles displayed completely normal spermatogenesis. The acute IF volume reduction and spermatogenic disruption in 5HT-treated rats were consistent with localized ischaemia due to constriction of the testicular arterial supply. The eventual increase in IF volume observed after 5HT treatment appeared to be secondary to the loss of germ cells. Although 5HT also inhibited pituitary LH release and Leydig cell steroidogenesis, these effects appeared to play only a minor role in the induction of spermatogenic damage.     

Gonadotrophin heterogeneity and biopotency: implications for assisted reproduction

The extensive heterogeneity of the gonadotrophin hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH), is due primarily to the heterogeneous nature of their carbohydrate side-chains, in particular sialic acid residues. In this review, we discuss the role of carbohydrate chains in receptor binding and activation, biological activity, and metabolic half-life. The synthesis and secretion of the various glycoforms of both FSH and LH appear to be under endocrine control with gonadotrophin-releasing hormone (GnRH), oestradiol and testosterone playing important roles. Evidence for different glycoforms having variable biopotency or different encoded functions is increasing, and the production and secretion of more or less acidic gonadotrophin species in different physiological states may represent an important mechanism whereby the pituitary regulates gonadal cell and organ function. This has potential importance for the development of new pharmaceutical reagents and new therapeutic regimens in assisted reproduction. It is envisaged that the use of existing and new forms of FSH/LH will allow patients to be treated in a more controlled and physiological manner, with treatment regimens individualized to the needs of the patient.     

Reproductive hormone profile among pesticide factory workers

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, as well as urinary levels of FSH, LH, and E1C, a metabolite of testosterone, were measured to investigate the adverse reproductive effects of organophosphate pesticides among Chinese factory workers who were occupationally exposed to ethylparathion and methamidophos. Thirty-four exposed workers were randomly chosen and recruited from a large pesticide factory, and 44 unexposed workers were selected from a nearby textile factory. A quantitative pesticide exposure assessment was performed among a subset of the exposed and unexposed workers. Information on potential confounders was collected in an interview. A single blood sample was collected at the end of a work shift, when each subject also donated a semen sample. Three first-voided urine samples were collected from each worker on 3 consecutive days. Urinary p-nitrophenol level at 1 hour after the work shift correlated with serum (r = 0.71, P < 0.01) and urinary (r = 0.51, P = 0.04) FSH levels. Stratifying by the subjects' exposure status, we found a significant negative correlation among the exposed group between urinary FSH level and sperm count (r = -0.61, P < 0.01) and between urinary FSH level and sperm concentration (r = -0.53, P = 0.03). Pesticide exposure alone was significantly associated with serum LH level (beta [coefficient of exposure effect] = 0.79; 95% confidence interval [CI] = 0.42, 1.16) but not with serum FSH or testosterone or with any urinary hormone levels. With adjustment for age, rotating shift work, current cigarette smoking, and current alcohol consumption, exposure significantly increased the serum LH level by 1.1 mIU/mL (95% CI = 0.34, 1.82). Meanwhile, the serum FSH level was slightly elevated (beta [coefficient of exposure effect] = 1.38; 95% CI = -0.09, 2.85) and the serum testosterone level was decreased (beta = -55.13; 95% CI = -147.24, 37) with increased pesticide exposure. Age and rotating shift work appeared to act as confounders. We conclude that organophosphate pesticides have a small effect on male reproductive hormones, suggestive of a secondary hormonal disturbance after testicular damage.