Reproductive tissue activity in hypothyroid or heat stressed hens

The ability of the reproductive tract of the White Leghorn hen under heat stress or methimazole thyroid blockage to assimilate 32P was examined. Both treatments increase the uptake of 32P by the shell gland and egg shell but only heal stress increases 32P uptake by the ovaries and reduces shell thickness. The greater shell thinness under the heat stress is related to an increased deposition of phosphate in the shell. Gilbert (1967) has reported an increased serum calcium, due to calcification inhibitions by phosphate, leading to an increased gonadotropin secretion. Thyroid blockage appears to stimulate TSH and gonadotropin LH secretion but in the absence of phosphate inhibition of calcification shell thickness is not affected. It is also speculated that hypothyroidism does not stimulate FSH secretion and therefore ovarian tissues is not activated by this condition.     

Improvement in gonadotropin secretion after corticosteroid therapy in a case of POEMS syndrome

We report a case of POEMS syndrome with various endocrine dysfunctions. A 49-year-old man was admitted to our hospital for pretibial edema and general fatigue. He had weakness of the lower extremities, hepatomegaly, monoclonal protein (IgG-lambda type), impotence, pigmentation and hypertrichosis. Endocrinological examination revealed impaired glucose tolerance, primary hypothyroidism and hypogonadotropic hypogonadism. After three months of treatment with corticosteroids, he showed an improvement in gonadotropin secretion, but no considerable change in the secretion of the other hormones. To our knowledge, this is the first case that showed an improvement in gonadotropin secretion as a result of corticosteroid therapy in POEMS syndrome.     

Thyrotropic deficiency

Central hypothyroidism (thyrotropic deficiency) is due to a defect in TSH secretion by thyrotrophs (or alternatively to an altered bioactivity of TSH). Central hypothyroidism is rare and is often associated with other pituitary deficiencies as it is generally encountered in case of hypothalamo-pituitary tumoral process. Clinical symptoms are milder than those of primary thyroid failure. Diagnosis is based on free T4 measurement whose level is decreased while TSH concentration is normal or minimally increased, reflecting an alteration in the bioactivity of TSH. Replacement therapy is monitored by T4 level measurement: the objective is to obtain normal T4 levels. TSH concentration must not be taken into account for the adjustment of the thyroxine doses.     

Reproductive effects of nontesticular illness

Diseases in other organs may impair the male reproductive system. Acute critical conditions such as severe trauma, surgery, myocardial infarction, burns, liver failure, intoxication, or starvation are associated with suppression of gonadotropin secretion and secondary hypogonadism. With chronic illnesses, a primary testicular disorder with elevated gonadotropin levels may occur. This may be associated with increased peripheral conversion of androgens to estrogens, resulting in clinical presentation of combined androgen deficiency and estrogen excess. The association of hypogonadism and feminization with cirrhosis of the liver is a classic example. Types of hypogonadism that may occur with chronic anemia, chronic renal failure, chronic spinal cord injury, thyroid diseases, Cushing's syndrome, diabetes mellitus, obesity, HIV infection, neoplasia, and other chronic illnesses are also described. Numerous drugs have side effects on the reproductive system.     

Induction of menstruation with bromocryptine in patients with euprolactinemic amenorrhea

Three nulliparous women presented with secondary amenorrhea with no evidence of endocrinopathy and normal skull x-ray. Pulsatile gonadotropin secretion was reduced, but an adequate pituitary gonadotropin reserve was demonstrable with luteinizing hormone-release factor provocation. The administration of bromocryptine was associated with amplification of pulsatile secretion of gonadotropins and was followed, in two of the three, by ovulatory menstruation. It is suggested that bromocryptine should be considered for induction of menstruation in euprolactinemic secondary amenorrhea.     

Hypothalamus-pituitary-ovarian axis in cyclic rats lacking progesterone actions

Antagonizing diestrous progesterone actions in cyclic rats by s.c. injections of the antiprogesterone RU486 (2 mg twice a day from metestrus through proestrus) increased LH and decreased FSH basal serum concentrations. Ovariectomy at metestrus (0800 h) increased serum levels of both gonadotropins in controls and reversed the RU486-induced dissociation of basal gonadotropin secretion. RU486-dissociated gonadotropin secretion is also dependent upon LHRH, since treatment (s.c.) with 1 mg GnRH antagonist (ORG 30276) twice a day on metestrus and diestrus completely prevented both the RU486-induced increase in LH and the decrease in FSH serum concentrations. The LHRH content in the medial basal hypothalamus and median eminence increased on proestrous morning in RU486-treated rats. The LH pituitary response to an exogenous i.v. bolus of 25 ng LHRH (Peninsula 7201; Peninsula Laboratory, Inc., Merseyside, UK) at 1700 h on diestrus was enhanced in rats treated with RU486. No differences in pituitary FSH response were noted with respect to oil-injected rats. The pituitary content of both gonadotropins decreased in RU486-treated rats on proestrous morning. All these effects due to RU486 in cyclic rats were reversed by ovariectomy. Testosterone serum levels increased significantly from diestrus onward, and the estradiol concentration increased on proestrous morning in RU486-treated rats. Ovariectomy as well as LHRH antagonist treatment eliminated the effects of RU486 on ovarian steroid production. Moreover, antiestrogen tamoxifen treatment reversed RU486-dissociated gonadotropin secretion, while antiandrogen flutamide treatment had no effect. The results of this experiment have confirmed previous findings that RU486 treatment dissociates basal gonadotropin secretion in cyclic rats. In addition, the present results show that: (1) this effect of RU486 is not due to a direct effect of this compound or to the blockade of progesterone action at a central level; (2) the effect of RU486 on pituitary gonadotropin secretion depends on ovarian substances other than progesterone and LHRH, since it is reversed by ovariectomy and completely abolished by LHRH antagonist treatment; (3) the reduction in FSH serum levels in rats treated with RU486 seems to be exerted by inhibin and estradiol at the pituitary level by reducing FSH synthesis and secretion; and (4) the hypersecretion of LH in rats treated with RU486, as compared to that resulting from ovariectomy, seems to be the consequence of, first, a lack of progesterone inhibitory action on LH secretion, and, second, an inappropriate feedback system involving increased hypothalamic LHRH activity and pituitary sensitivity to LHRH of moderately high levels of estradiol in the presence of abnormally high levels of testosterone.     

Low T3 syndrome

Many nonthyroidal illnesses are associated with reduced serum T3 and, in more severe conditions, T4 concentrations, without increased serum TSH secretion. The term euthyroid sick syndrome (ESS) identifies these low T3 and low T3-T4 states. It may be difficult to exclude central hypothyroidism in patients admitted to medical intensive care units. The mortality rate has been found to be inversely correlated with the serum T4 concentration. These abnormalities are a consequence of altered hepatic T3 production from T4 (through type 1 5'-desiodase inhibition), T4 serum protein binding and hepatic transport, and TSH secretion. Many mediators and drugs are involved in the pathogenesis of ESS. The role of cytokines has recently been emphasized. It remains unclear whether ESS represents a physiological protective mechanism, or a damaging maladaptative response and whether early thyroid hormones administration might improve survival in severe non thyroidal conditions.     

Nursing home admission for the elderly and chances for avoiding admission. Results of a representative study of facilities for inpatient nursing care

We studied the possible role of nitric oxide (NO) in GnRH-induced gonadotropin secretion in the female water frog, Rana esculenta. During pre-reproduction, pre-ovulation, ovulation, post-ovulation, refractory, recovery and hibernation, pituitaries were incubated with medium-alone, GnRH, NO donor (NOd), NO synthase inhibitor (NOSi), cyclic GMP analogue (cGMPa), soluble guanylate cyclase inhibitor (sGCi), GnRH plus NOSi, GnRH plus sGCi, and NOd plus sGCi. Because antisera raised against gonadotropins are not available for this species, we measured these hormones indirectly through their effects on ovarian progesterone secretion. The ovaries were superfused with the pituitaries pre-incubated as reported above. In addition, NOS activity and cGMP levels were determined in the pre-incubated pituitaries. Those pre-incubated with medium-alone and with GnRH increased progesterone secretion during pre-reproduction, pre-ovulation, ovulation and recovery; the increase induced by GnRH was higher than that induced by medium-alone during pre-reproduction, pre-ovulation and recovery. NOd and cGMPa increased progesterone in all considered reproductive phases except ovulation; the increase induced by NOd and cGMP was higher than that induced by medium-alone during pre-reproduction, pre-ovulation and recovery. NOS activity was highest during ovulation and lowest during post-ovulation, refractory and hibernation. GnRH increased NOS activity during pre-reproduction, pre-ovulation and recovery. Cyclic GMP levels were highest during ovulation and lowest during post-ovulation, refractory and hibernation. GnRH increased cGMP levels during pre-reproduction, pre-ovulation and recovery, NOd during all considered reproductive phases. These results suggest that NO mediates basal and GnRH-induced gonadotropin secretion in female Rana esculenta.     

Alcohol on campus: alcohol-related emergencies in undergraduate college students

Lithium is used in the prophylaxis of bipolar depressive disorder in augmentation treatment of depression and in the therapy of some cases of unipolar depression. Lithium affects cell function via its inhibitory action on adenosine triphosphatase (ATPase) activity, cyclic adenosine monophosphate (cAMP), and intracellular enzymes. The inhibitory effect of lithium on inositol phospholipid metabolism affects signal transduction and may account for part of the action of the cation in manic depression. Lithium also alters the in vitro response of cultured cells to thyrotropin-releasing hormone (TRH) and can stimulate DNA synthesis. Lithium is concentrated by the thyroid and inhibits thyroidal iodine uptake. It also inhibits iodotyrosine coupling, alters thyroglobulin structure, and inhibits thyroid hormone secretion. The latter effect is critical to the development of hypothyroidism and goiter. Effects on brain deiodinase enzymes and alterations in thyroid hormone receptor concentration in the hypothalamus are under investigation in relation to the therapeutic effect of lithium. The ion affects many aspects of cellular and humoral immunity in vitro and in vivo. This accounts for a rise in antithyroid antibody titer in patients having these antibodies before lithium administration whereas there is no induction of thyroid antibody synthesis de novo. Goiter, due to increased thyrotropin (TSH) after inhibition of thyroid hormone release, occurs at various reported incidence rates from 0%-60% and is smooth and nontender. Subclinical and clinical hypothyroidism due to lithium is usually associated with circulating anti-thyroid peroxidase (TPO) antibodies but may occur in their absence. Iodine exposure, dietary goitrogens, and immunogenetic background may all contribute to the occurrence of goiter and hypothyroidism during long-term lithium therapy. It is currently unclear whether the reported association of lithium therapy and hyperthyroidism are causal, although there is suggestive epidemiological evidence. Finally, lithium therapy is associated with exaggerated response of both TSH and prolactin to TRH in 50%-100% of patients, although basal levels are not usually high. It is probable that the hypothalamic pituitary axis adjusts to a new setting in patients receiving lithium.     

Different hCG assays to measure ectopic hCG secretion in bladder carcinoma patients

We evaluated the clinical performance of assays measuring intact human chorionic gonadotropin alone (i-hCG), intact and nicked human chorionic gonadotropin (i-hCG and hCGn), free beta-subunit (free beta-hCG) and total beta-human chorionic gonadotropin (t-hCG) using different commercial kits, in a group of bladder carcinoma patients with ectopic human chorionic gonadotropin (hCG) secretion, at diagnosis and during treatment. The diagnostic sensitivity obtained ranged between 63.6% and 75.7% (t-hCG assays), 72.7% (free beta-hCG assay), 18.2% (i-hCG and hCGn) and 6% (i-hCG assay). Median increases of hCG during treatment in patients with chemotherapy resistance ranged from 4.9 to 6.9 for t-hCG and free beta-hCG assays and from 1.4 to 3.2 for i-hCG and i-hCG plus hCGn assays. Median decreases when chemotherapy was efficient ranged from 2.8 to 3.3 (t-hCG and free beta-hCG assays) and from 1.1 to 1.5 (i-hCG and i-hCG plus hCGn assays). We conclude that t-hCG and free beta-hCG are the most suitable assays for the management of bladder carcinoma patients as the ectopic secretion of chorionic gonadotropin is mainly due to the free beta-subunit.     

Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone

In the United States, ovarian cancer is the fourth most frequent cause of cancer death among women, following lung, breast, and colorectal cancers. Each year, approximately 26,000 women are diagnosed with ovarian cancer and 14,000 die of it. Germline mutations in BRCA1, BRCA2, or other genes have been implicated in a small fraction of cases. However, it has been suggested that, for the great majority of patients, the risk of epithelial ovarian cancer could be related to "incessant ovulation" (i.e., to the chronically repeated formation of stromal epithelial clefts and inclusion cysts following ovulation) or to some type of hormonal stimulation of ovarian epithelial cells, either on the surface of the ovary or within ovarian inclusion cysts, possibly mediated through excessive gonadotropin secretion. From the evidence to date, the relative importance of these two hypotheses--incessant ovulation and gonadotropin stimulation--cannot be distinguished. While either or both may play a role in the development of ovarian cancer, it appears that an additional major factor must also be involved. The purpose of this review is to evaluate evidence for and against the incessant ovulation and gonadotropin hypotheses, as well as to consider the possibility that risk of ovarian cancer may be increased by factors associated with excess androgenic stimulation of ovarian epithelial cells and may be decreased by factors related to greater progesterone stimulation. Many features of the evidence bearing on the pathophysiology of ovarian cancer appear to support a connection with androgens and progesterone.     

Improved and effective assays of the glutamic oxaloacetic transaminase by the coenzyme-apoenzyme system (CAS) principle

257 patients have been reviewed 1-5 years (mean 3 years 2 months) after receiving one of five dose regimes of 125I for thyrotoxicosis. The cumulative incidence of hypothyroidism was 34% and of persistent thyrotoxicosis 17%. The group receiving doses between 351 and 500 muCi/g had the highest proportion of euthyroid patients (65%) with the lowest requirement for repeat therapy (46%). In the euthyroid patients, increasing dose of 125I was associated with progressive decline in mean thyroxine (T4) level and free thyroxine index (FTI) within the respective normal ranges, and increase in mean thyroid stimulating hormone (TSH) level to above the normal range. Euthyroid patients with elevated TSH levels had significantly lower T4 and FTI values compared with those with normal TSH, and showed a 3-4-fold increased rate of development of hypothyroidism over 1 year. Euthyroid patients with elevated T3 levels remained euthyroid during the subsequent year and mean T3 levels declined significantly, suggesting that abnormally elevated T3 levels after 125I do not generally indicate impending relapse of thyrotoxicosis. It is concluded that the potential admantages of 125I therapy for thyrotoxicosis in reducing the incidence of hypothyroidism have not been realized in practice.     

Evidence for a role for the cyclic adenosine 3',5'-monophosphate/protein kinase-A pathway in regulation of the gonadotropin subunit messenger ribonucleic acids

cAMP regulation of gonadotropin secretion and subunit mRNA levels was studied in pituitary cells perifused with pulses of GnRH. Pituitary cells from 7-week-old male rats castrated at 5 weeks of age were stimulated hourly for 9-24 h with 1-min pulses of GnRH, the adenylate cyclase activator forskolin, the cell-permeable cAMP analog 8-bromo-cAMP (8Br-cAMP), or control medium. Cells were also treated with the nonsteroidal antiinflammatory drug flufenamic acid, which reduces pituitary cAMP levels. During perifusion, the effluent was collected in 10-min fractions for FSH and LH assay. At the completion of perifusion, total RNA was extracted, and gonadotropin subunit mRNA levels were quantitated by Northern analysis. Continuous administration of flufenamic acid gradually reduced the amplitude of GnRH-stimulated FSH and LH pulses to nadir values of 40 +/- 4.7% and 62 +/- 12% of the control value, respectively. Flufenamic acid decreased (P < 0.05) FSH beta and alpha-subunit mRNA levels and blocked the effect of GnRH to lengthen LH beta mRNA. Pulses of forskolin or 8Br-cAMP released LH and FSH, and continuous forskolin or 8Br-cAMP potentiated the gonadotropin stimulatory effect of GnRH. Forskolin or 8Br-cAMP increased (P < 0.05) FSH beta mRNA and alpha-subunit mRNA levels when administered in pulses, but not when administered continuously, and lengthened LH beta mRNA. The Nal-Glu GnRH antagonist blocked the effects of GnRH pulses, but not the effects of 8Br-cAMP or forskolin. In conclusion, lowering intracellular cAMP levels with flufenamic acid attenuated GnRH-stimulated gonadotropin secretion, decreased alpha-subunit and FSH beta mRNA levels, and blocked the effect of GnRH to lengthen LH beta mRNA, whereas 8Br-cAMP or forskolin produced the opposite effect. These data extend previous results which suggested that cAMP modulates gonadotropin secretion and indicate that the cAMP/A-kinase pathway regulates each of the gonadotropin subunit mRNAs.     

Dynamics of growth hormone secretion in patients with primary hypothyroidism, before and after treatment with thyroideal hormones

Growth hormone (GH) secretion was studied in a group of alut controls and a series of patients with primary hypothyroidism before and after treatment with thyroid hormones. Intravenous insulin-induced hypoglycemia was the stimulus used (0,1 UI/kg body weight). It is concluded that in primary hypothyroidism, GH secretion is almost absent due to relative inactivity of the somatotropic cells and/or lack of GH-RH. This decreased secretory response becomes rapidly normal after treatment with physiological doses of thyroid hormones.     

Ovarian steroid modulation of neurokinin contents in hypothalamus, pituitary, trigeminal nucleus, and cervical spinal cord of the ovariectomized female rat

Ovariectomized rats were treated with estradiol benzoate (EB) and progesterone in conditions known to negatively and positively regulate gonadotropin secretion. Injection with EB decreased the plasma concentration of substance P at the time of the positive feed-back exerted by EB on gonadotropin secretion, while having no effect on the plasma concentration of neurokinin A. In the hypothalamus, EB injection enhanced the substance P and neurokinin A content, while progesterone reduced the substance P content. In the anterior pituitary, the substance P content was increased after progesterone, and this increase was blocked by EB. Conversely, in the posterior pituitary, the substance P content was reduced after progesterone, and this effect was enhanced by EB. In the trigeminal nucleus, the substance P content was increased after progesterone and EB, while only progesterone affected neurokinin A content. Finally, in the cervical spinal cord, the substance P and neurokinin A contents were reduced after EB. We conclude that neurokinin contents are controlled by ovarian steroids not only in the hypothalamo-pituitary complex but also in the trigeminal nucleus and the cervical spinal cord.     

Optimizing sampling strategies for estimating quality-adjusted life years

Ovarian organ culture was used to study the influence of various gonadotropin hormones (100 ng FSH, 100 ng LH, 100 ng LH added together with 100 ng FSH; 1 i.u. hCG or 10 i.u. PMSG) on growth and development of follicles as well as on steroid secretion by ovaries of postnatal, 15-day-old mice. Ovaries were aseptically removed and single organs were placed on a piece of lens paper which was supported by a stainless steel grid in the small organ culture dish. The cultures were maintained in medium M199 supplemented with 5% of calf serum in a CO2 incubator at 37 degrees C. The morphological changes and steroid secretion measured by appropriate RIAs were studied. The stages of follicular development and the incidence of particular types of follicles were scored. Progesterone and estradiol were detected in the medium by radioimmunoassay. Differences between control and gonadotropin stimulated ovaries were found in the number of the ovarian follicles in more advanced maturation stages. There was increased number of multilaminar and antral follicles in FSH and FSH plus LH treated cells. The adding of gonadotropin hormones to the culture medium stimulated significantly progesterone secretion. The most significant effect was observed in media of cultures treated with LH and hCG. As to estradiol secretion the highest stimulatory effect was seen in cultures supplemented with FSH alone, together with LH and with PMSG. The organ culture technique applied in the current study could be a suitable model of studying the interaction of various factors as well as its effect on ovarian differentiation and on selection of dominant follicles. This system allows maintaining the structural integrity of the whole ovary, thus in the physiological functional status of the organ.     

Activin-like peptides in somatotrophs and activin stimulation of growth hormone release in goldfish

Activin and inhibin, dimeric protein hormones originally isolated from mammalian gonads, are involved in the regulation of pituitary gonadotropin secretion. Using domain-specific antibodies against activin and inhibin alpha, beta A, and beta B subunits, the present study demonstrates that immunoreactive activin and inhibin subunits, especially beta A, exist in goldfish pituitary. Immunocytochemical staining with anti-gonadotropin-II and anti-growth hormone showed that the pituitary cells containing immunoreactive activin beta subunits are somatotrophs. This is different from the situation in mammals where it is the gonadotrophs that produce activin molecules within the pituitary. The staining with anti-beta B was overall weak compared to that with anti-beta A, but both appear to localize in the same cells. Strong immunostaining with the anti-inhibin alpha subunit was also observed in the goldfish pituitary; however, the immunoreactivity is dissociated from those of beta A and beta B, and mainly associated with nerve fibers in the neurointermediate lobe. Based on this evidence, it is suggested that the goldfish pituitary predominantly produced activin-like molecules. Both porcine activin and inhibin stimulate growth hormone release from perifused goldfish pituitary fragments. Taken together with our previous findings that porcine activin stimulates gonadotropin-II release in goldfish, and the fact that the somatotrophs and gonadotrophs are in close contact with each other in the goldfish pituitary, it is hypothesized that somatotroph-derived activin may exert paracrine actions on the adjacent gonadotrophs to stimulate gonadotropin release and autocrine actions on somatotrophs to stimulate growth hormone secretion. This also provides a mechanism for communication between these two pituitary cell types.     

Massive ovarian enlargement in primary hypothyroidism

OBJECTIVE: To report a case of ovarian cyst formation and myxedematous infiltration of the ovary in a subject with primary hypothyroidism. DESIGN: Retrospective case report. SETTING: University hospital. PATIENT(S): A 16-year-old female adolescent with pelvic pain, galactorrhea, irregular menses, and ovarian cysts on pelvic examination. INTERVENTION(S): Laparotomy with bilateral ovarian wedge resection and thyroid replacement therapy. MAIN OUTCOME MEASURE(S): Ovarian histopathology, thyroid function tests, and menstrual history. RESULT(S): Resolution of patient's pain, galactorrhea, and resumption of normal menses. CONCLUSION(S): Ovarian cyst formation may accompany primary hypothyroidism in the child with accelerated or delayed sexual maturation. To date, the underlying pathophysiology of the morphological changes in the ovary remain enigmatic. This case report provides the first insight into the actual histologic changes that occur in ovaries of subjects with primary hypothyroidism without secondary ovarian pathology such as torsion. There is clear evidence of myxedematous infiltration into the ovarian stroma without luteinization of the theca interna. These microscopic findings suggest that local changes occurring independent of gonadotropin stimulation may contribute significantly to altered morphology of the ovaries in primary hypothyroidism.     

The hypothalamic-pituitary-luteal axis in women: effects of long-term orally active opioid antagonist (naltrexone) administration

Aim of our study is to assess the effect of a long-term oral opiate antagonist treatment during the luteal phase on the hypothalamic-pituitary-ovarian axis. Fourteen normovulatory women participated to the study. Immediately after the ovulation, the patients were randomly divided in two groups: in the first one women received naltrexone 50 mg/die orally (Antaxone Zambon Italy) from day 1 of the luteal phase for 7 days. In the second patients were treated with placebo for the same period and served as control group. On day 7, patients were hospitalized for a pulse pattern study followed by a GnRH test. LH, FSH, Estradiol, Progesterone were assayed. The naltrexone administration strongly increased the number as well as the amplitude of the gonadotropin pulses. The circulating P levels were also significantly higher in treated patients. The GnRH injection significantly increases the gonadotropin secretion in all patients. The stimulated LH and FSH secretion was significantly greater in treated patients when compared to controls. Such discharge of LH determined a significant increase of progesterone production in controls, but failed to stimulate the corpus luteum in treated patients. In conclusion the present paper strengthen an important role of the opioidergic system in the regulation of GnRH pulsatility in luteal phase. Moreover, our findings confirms the sensibility of the corpus luteum to LH and the possibility to stimulate the P secretion during the luteal phase.