Control of cell growth. II. Requirement of thyroid hormones for the in vivo estrogen-dependent growth of rat pituitary tumor cells

A subclone of rat pituitary tumor cells, designated GH3/C14, was isolated from the parent population of GH3 pituitary cells and was estrogen-dependent for growth in vivo. GH3/C14 cells inoculated into host animals formed tumors in intact females, estrogen-treated ovariectomized females, and estrogen-treated males, but not in untreated intact or castrated males, or untreated ovariectomized females. Exogenous treatment with estrogens supported tumor formation in male animals. Radioimmunoassay of the average serum estradiol concentrations that support tumor growth in intact females, estradiol-treated intact females, and estradiol-treated intact males gave values of 41 +/- 4, 1,130 +/- 150, and 730 +/- 140 pg/ml, respectively. Tumor formation by GH3/C14 cells inoculated into male animals was not supported by either exogenous progesterone or hydrocortisone acetate. Further, these two steroid hormones had no significant effect on the estrogen-promoted growth in males or females. Exogenous testosterone treatment promoted tumor formation in males and ovariectomized females, but dihydrotestosterone was completely ineffective. Radioimmunoassay of the serum from tumor-bearing animals and the medium from the cells in culture showed that the cells produced growth hormone in vivo and in vitro but did not produce measurable amounts of luteinizing hormone or follicle-stimulating hormone. The groth of GH3/C14 cells in culture was examined in medium without added estrogen, and with estradiol added to the level of either the normal intact female rat or the estradiol-treated animals. No direct growth stimulation by estrogens could be detected in culture; the data suggested an indirect growth control mechanism.     

Regulation of sulfotransferase mRNA expression in male and female rats of various ages

Sulfotransferases (SULTs) are Phase II drug-metabolizing enzymes that catalyze the addition of a sulfuryl moiety to both endogenous compounds, including steroids and neurotransmitters, and certain xenobiotics, including N-hydroxy-2-acetylaminoflourine and phenolic compounds, like alpha-naphthol. In contrast to certain Phase I drug-metabolizing enzymes, little is known about the regulation of the sulfotransferases. These series of studies were designed to analyze SULT mRNA expression and hormonal regulation in male and female rats. The hepatic expression of six different SULT isoforms was examined including three phenol SULTs and three hydroxysteroid SULTs. SULT mRNA expression was examined in adult and developing rats, as well as, in hypophysectomized (HX) and growth hormone-supplemented HX animals. SULT1A1 is thought to be important for the sulfation of simple phenols and its mRNA expression is about twice as high in adult male as in female rats. This difference in SULT1A1 mRNA levels is largely due to a greater decrease in mRNA levels after puberty in female than in male rats. Hypophysectomy resulted in a decrease in expression of SULT1A1 mRNA in both male and female rats. Replacement of growth hormone (GH) by either intermittent injection (male pattern) or infusion (female pattern) failed to restore SULT1A1 expression. Sulfotransferase SULT1C1 has been implicated in activation of N-hydroxyacetylaminoflourine. In contrast to SULT1A1, SULT1C1 mRNA expression is about 10-fold higher in adult males than in adult female rats. This male-dominant expression pattern emerges at 40-50 days of age and is due to an increase in SULT1C1 mRNA in males. Hypophysectomy abolished SULT1C1 expression in male rats. Interestingly, replacement of GH by injection (male pattern) restored SULT1C1 mRNA expression in males and enhanced SULT1C1 expression in female rats to levels observed in adult male rats. GH infusion (female pattern) did not affect SULT1C1 mRNA expression in either male or female rats. Estrogen sulfotransferase (SULT1E2) may play a role in estrogen homeostasis. Adult male rats express SULTIE2 mRNA at levels 10-fold higher than those observed in adult females and similar to SULT1C1, this is due to an increase in SULT1E2 mRNA occurring during puberty in the male rat. Hypophysectomy did not appreciably affect SULT1E2 expression in male rats, however in contrast to males, hypophysectomy markedly enhanced SULT1E2 expression in female rats. GH infusion suppressed SULT1E2 levels in HX male rats. The expression of hydroxysteroid sulfotransferases was also examined. The SULT-20/21 isoform was expressed in both male and female rats. Male expression of this isoform peaked at 30 days of age and then declined to approximately 30% of the level observed in adult females. SULT-20/21 mRNA expression increased sharply at 45 days of age in female rats and remained elevated. Expression of SULT-20/21 mRNA was decreased markedly by hypophysectomy in both male and female rats. GH injection did not affect SULT-20/21 mRNA expression in HX males, however this treatment resulted in a 4-fold increase in SULT-20/21 mRNA in HX females. GH infusion restored SULT-20/21 expression in HX-male rats. GH infusion did elevate SULT-20/21 mRNA expression in female-HX rats, but not to the level observed in intact females. Hydroxysteroid SULT isoform SULT-40/41 was expressed in adult female but not adult male rats. SULT-40/41 expression peaked at 15 days of age in both male and female rats and decreased thereafter. The decrease in expression was more pronounced in male rats. SULT-60 mRNA, like SULT-40/41, was expressed only in adult female rats. Male rats express SULT-60 at 30 days of age, but SULT-60 mRNA is undetectable at 60 days. SULT-60 mRNA was expressed in females only after day 30 and female SULT-60 mRNA expression remains high thereafter. SULT-40/41 and SULT-60 mRNA expression was increased by HX in male rats and decreased by HX in female rats. (ABSTRACT TRUNCATED)     

Effects of iodinated contrast agents in MR imaging

At least two classes of mRNA for the GH receptor (GHR) and GH binding protein (GH BP) with different 5' untranslated first exons exist in the rat. One such class, the GHR1 is predominantly expressed in the liver of female rats. The hepatic expression of the GHR1 mRNA in normal and hypophsectomized rats of both sexes was studied by employing an RNase protection/solution hybridization assay. Normal females expressed 10-fold more GHR1 mRNA than males, hypophysectomy of female rats decreased the GHR1 level to that observed in male rats. Continuous GH treatment of hypophysectomized male and female rats for 6 days increased the expression of GHR1 mRNA to levels found in normal females, whereas intermittent GH treatment without effect. Bovine GH(bGH) induced the GHR1 expression in a time- and dose-dependent manner in primary cultures of adult rat hepatocytes as determined by solution hybridization. Maximal induction was achieved after 72 h of treatment with 50 ng bGH/ml medium. Female enriched expression of receptor and binding protein mRNAs raises the possibility that they participate in determining the ability of the liver to respond differently to the male and female GH secretory patterns. Our in vitro model utilizing cultures of primary adult rat hepatocytes could be used to address this issue as well as explore a hormonal interplay in regulation of GHR1 expression.     

Adenovirus-mediated in vivo gene transfer and expression in normal rat pancreas

Growth hormone (GH) secretion declines during normal aging along with reproductive activity in mammalian species. Various behavioral changes also occur in aged animals. In these experiments we have studied the effects of GH administration on behavioral and endocrine alterations exhibited by aged (18 months old) female rats of the Sprague-Dawley strain. Animals were selected showing at least 2 weeks of cornified vaginal smears (constant estrous) and treated with GH (0.1 mg/kg SC) daily for 8 weeks. Vaginal smears performed during the drug treatment revealed a recovery of estrous cycle in 60% of animals. GH treatment was also followed by an increased acquisition of shuttle-box active avoidance behavior and a facilitated retention of passive avoidance response. Compared to saline-injected controls, female rats treated with GH also exhibited a decrease of novelty-induced excessive grooming. The endocrine pattern of GH-treated aged female rats revealed a decrease in plasma prolactin levels and an increase in luteinizing hormone and 17 beta-estradiol levels as compared to those of control animals. These results support the concept that behavioral and endocrine alterations occurring in aging are not irreversible and that GH may interfere with these changes probably by means of its trophic action on different target organs.     

Effects of sex hormones on protein and collagen content of the temporomandibular joint disc of the rat

PURPOSE: The effect of sex hormones on the protein and collagen content of the temporomandibular joint (TMJ) disc of adult male and female rats. MATERIALS AND METHODS: One hundred forty-four Wistar rats were assigned to 14 groups of 12 each. Two groups, one female and one male, served as a control and received no treatment, and two other groups (one female and one male) received a sham gonadectomy and placebo hormone. The remaining 10 groups (five males and five females) received either orchiectomy or ovariectomy, followed by administration of estrogen, progesterone, combined estrogen and progesterone, or testosterone. The total protein and collagen content of the TMJ disc were determined using the calorimetric hydroxyproline method. RESULTS: The collagen content of TMJ discs of control males was statistically greater than the collagen content of the control female rats. This difference disappeared after ovariectomy of females and orchiectomy of males. Also, there was a general trend for a decrease in collagen and protein content to be produced by estrogen, progesterone, and by estrogen combined with progesterone in castrated male and female rats, and by orchiectomy of male rats. There was also a trend toward an increase in collagen and protein content after ovariectomy in female rats and administration of testosterone to castrated male and female rats. However, the only statistically significant effect of the drugs tested was that of estrogen combined with progesterone in ovariectomized female rats (a lowering effect on the total protein) and of estrogen alone in orchiectomized male rats (a lowering effect on the collagen content). CONCLUSION: Steroid sex hormones have an effect on the collagen and protein content of the TMJ disc of the rat as indicated by the difference in the values between control males and females and by the disappearance of this difference on castration of both male and female animals. This was also manifested by the significant effect of estradiol on collagen content of castrated males, by the effect of estrogen combined with progesterone on the protein content of castrated females.     

Effects of growth hormone secretagogues on prolactin release in anesthetized dwarf (dw/dw) rats

In addition to stimulating GH release, GH secretagogues such as GH-releasing peptide-6 (GHRP-6) stimulate small amounts of ACTH and PRL release. Although the effects on ACTH have recently been studied, there is little information about the effects of GHRP-6 on PRL. We have now studied GHRP-6-induced GH and PRL release and their regulation by estrogen (E2) in anesthetized male and female rats and in GH-deficient dwarf (dw/dw) rats that maintain high pituitary PRL stores and show elevated hypothalamic GH secretagogue receptor expression. Whereas GHRP-6 (0.1-2.5 microg, i.v.) did not induce PRL release in normal male or female rats, significant PRL responses were observed in dw/dw females. These responses were abolished by ovariectomy and could be strongly induced in male dw/dw rats by E2 treatment. These effects could be dissociated from GHRP-6-induced GH release in the same animals, but not from PRL release induced by TRH, which was also abolished by ovariectomy and induced in males by E2 treatment. However, the effects of GHRP-6 on PRL were unlikely to be mediated by TRH because in the same animals, TSH levels were unaffected by GHRP-6 whereas they were increased by TRH. The increased PRL response could reflect an increase in GH secretagogue receptor expression that was observed in the arcuate and ventromedial nuclei of E2-treated rats. Our results suggest that the minimal PRL-releasing activity of GHRP-6 in normal rats becomes prominent in GH-deficient female dw/dw rats and is probably exerted directly at the pituitary; these GHRP-6 actions may be modulated by E2 at both hypothalamic and pituitary sites.     

Age and gender influence basal and stress-modulated hypothalamic-pituitary-thyroidal function in Fischer 344/N rats

To investigate possible gender- and age-associated changes of the hypothalamic-pituitary-thyroid (HPT) axis at baseline and during stress, we studied healthy young (3-month) and old (23-month) female 344/N Fischer rats at the basal state and after 2 h of immobilization (IMMO), in parallel to age-matched male rats. At baseline, there were no major differences on HPT axis functions between young female and male animals. Old age was associated with impaired central thyroid function in both genders, albeit to a much lesser extent in females than in males. Plasma prolactin (PRL) levels were similar in young females and males but were higher in old females than males. IMMO inhibited HPT axis functions in both genders in young, but not old animals. Thus, plasma TSH and hypothalamic TRH mRNA levels were decreased by IMMO in young, but not in old rats of both genders. IMMO increased plasma PRL in young and old males, but did not have any effect in young and old females. In summary, these data indicate that age and gender exert diverse effects on HPT axis functions at baseline and after stress.     

Effects of chronic systemic administration of 5-HT on food intake and body weight in rats

The effects of chronic peripheral administration of 5-HT on food intake and body weight was investigated. In normal male Wistar rats, normal female Wistars, obese Zucker males, ovariectomised Wistar females, or normal Wistar males free fed a cafeteria diet, suppression of the creeping weight gain typical of control animals is observed. In females, this effect is not dependent on the local hormonal environment, because intact and ovariectomised females showed similar responses to treatment. One sex difference is that the weight suppressive effect in males is accompanied by an anorectic effect, whereas this anorectic effect is absent in females. Thus, although reduced food intake may partially explain the suppression of weight gain in males, in females it must be due to other, perhaps metabolic, effects. It is possible that these metabolic effects may also occur in males, suggesting one possible explanation of why the effect was typically larger in males than females.     

The use of intermittent lighting in broiler raising. 2. Effects on the somatotrophic and thyroid axes and on plasma testosterone levels

Male and female broiler chicks were raised separately in nearly continuous lighting [23 h light (L):1 h dark (D), CL] and consumed feed ad libitum. At 7 d of age, the intermittent lighting schedule (1L:3D, IL) was imposed on half of the chicks, whereas the other chicks remained under CL. In addition to performance characteristics, several parameters of the somatotrophic and thyrotrophic axes were studied together with plasma concentrations of testosterone. Males had a higher growth rate than females regardless of the imposed lighting schedule and this pronounced growth difference is reflected by higher plasma concentrations of growth hormone (GH), and a better GH receptor occupancy. Differences in growth rate between sexes could not be attributed to differences in circulating 3,3',5-triiodothyronine (T3) levels or to hepatic deiodination activities. However, from 3 wk of age onwards, males had significantly higher plasma testosterone levels than females. Plasma GH and T3 levels decreased whereas plasma insulin-like growth factor-I and thyroxine levels increased with age in all experimental groups. The age-related decline in plasma GH levels were less pronounced for males than for females. No major changes in other hormonal parameters or deiodination activities could be observed as a result of imposing IL, except for the higher plasma GH levels of IL chickens, and for plasma testosterone concentrations in IL males at Day 41, which were twice the levels found in their CL counterparts. These results therefore suggest that the somatotrophic axis as well as circulating testosterone levels mediate the sex-related differences in growth rate and the compensatory growth as present in males.     

Gender comparisons of the mechanomyographic responses to maximal concentric and eccentric isokinetic muscle actions

PURPOSE: The purpose of this study was to determine whether there is a gender difference in the velocity-related patterns of mechanomyographic (MMG) responses to maximal isokinetic concentric (CON) and eccentric (ECC) muscle actions. METHODS: Adult males (N = 15) and females (N = 16) performed maximal CON and ECC muscle actions of the leg extensors on a calibrated Cybex 6000 dynamometer at velocities of 30, 90, and 150 degrees.s-1. MMG was detected by a piezoelectric crystal contact sensor placed over the vastus lateralis muscle. RESULTS: The results indicated that there were decreases in CON peak torque (PT) across velocities, while ECC PT remained constant with increasing velocity for both genders. MMG amplitude increased significantly (P < 0.05) with velocity in both the males and females for CON and ECC muscle actions. There was a gender difference in the velocity-related patterns of MMG responses to maximal isokinetic CON muscle actions; however, there was no gender difference in the pattern of ECC MMG responses. CONCLUSIONS: The gender difference in CON MMG responses may be attributed to the greater percent decline in CON PT across velocity for the females than the males. In addition, the males displayed greater CON and ECC MMG amplitudes at all muscle action velocities than the females, possibly because of gender differences in muscle mass and/or thickness of the adipose tissue layer.     

Aged-rodent models of long-term growth hormone therapy: lack of deleterious effect on longevity

Studies were carried out to examine the effects of long-term recombinant human growth hormone (GH) therapy on longevity in rodents. In the first study, 150 18-month-old female F344 rats were divided into three groups of 50 rats per group: Group 1, solvent vehicle; Group 2, 10 microg GH/kg body weight three times per week; Group 3, 50 microg GH/kg body weight three times per week. GH and solvent vehicle therapies were started at 18 months of age and continued until all the animals died spontaneously. Serum insulin-like growth factor (IGF)-I was measured at 18 and 29 months of age and on 3-month-old rats. Serum IGF-I level decreased between 3 and 29 months of age. GH therapy reversed the decrease in a dose-dependent manner, with the 50 microg GH dose returning the serum IGF-I level to that of 3-month-old animals. However, statistical analysis revealed no significant effect of GH therapy on median life span, 10th percentile life span, or maximum life span. Similar observations on longevity were made on aged F344 male rats and on aged Balb/c mice, even when the dose of GH was increased to 1.0 mg/kg body weight two times per week. The main pathologic lesions in control animals were nephropathy, cardiomyopathy, leukemia, and testicular interstitial cell tumor; the prevalence of these lesions was not significantly altered by GH therapy. We conclude that long-term low-dose GH therapy that includes doses in the range that is given to humans in clinical trials in GH deficiency and to revert age-related physiologic declines has no overt deleterious effects on longevity and pathology in aged rodents.     

Communal reproductive success in rats (Rattus norvegicus): Effects of group composition and prior social experience.

Compared the reproductive success and maternal behavior of sibling pairs of female Long-Evans rats (Rattus norvegicus) housed together from birth (familiar) to that of pairs of unrelated females housed apart during development (unfamiliar). Sires either remained in the colonies through weaning of their pups or were removed before parturition. Familiar animals reared more pups to weaning, were more likely to share in caring for pups, and were less likely to exhibit infanticide than were unfamiliar ones. The presence of males in cages with pups had no direct effect on the reproductive success of females, but female pairs housed with males spent less time than female pairs housed alone caring for pups together in a combined nest. Conflicting evidence for communal rearing in populations of wild rats may reflect differences in the genetic relatedness or early social experience of female rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Severe experimental uraemia does not decrease the population of rat pituitary somatotrophs

BACKGROUND: Growth hormone (GH) secretion by the anterior pituitary has been shown to be depressed in severely uraemic rats. Changes in the population of pituitary somatotrophs might be partially responsible for this decrease. METHODS: To analyse the population of pituitary somatotrophs in severe uraemia, immunocytochemical detection and quantification of GH-producing cells were carried out on paraffin sections from young rats either 5/6 nephrectomized, sham-operated fed ad libitum or sham-operated pair-fed with the nephrectomized animals. Results: Nephrectomized rats were severely uraemic and growth retarded. The overall cell density (total pituitary cells/mm2) was higher in 5/6 nephrectomized animals in comparison with the two sham-operated groups. Thus, although the percentage of GH cells was slightly lower in nephrectomized than in control rats, no difference in either the density (cells/mm2) or the cross-sectional area of GH cells was found among groups. CONCLUSIONS: These results suggest that severe experimental uraemia interferes with the maturation process of the pituitary gland and support the contention that differences in either the number or the size of pituitary somatotrophs cannot explain the reduced GH secretion previously reported in severely uraemic rats.     

Micro and macro perspectives in auxology: findings and considerations upon the variability of short term and individual growth and the stability of population derived parameters

The present paper links the two most contrasting aspects of auxology, and addresses the apparent discrepancy between the variability and pulsatility of short term individual growth, and the stability of population derived parameters. When body stature is measured at monthly intervals, an irregular incremental pattern becomes obvious, with a number of large scale components such as series of prepubertal and pubertal growth spurts, seasonal influences on height gain, and influences of the psychosocial and economic background. When measurement intervals decrease, the patterns of stature increment appear even more irregular, and a number of short scale components become apparent, that are distinct from measurement error. Observations are presented that suggest growth being a pulsatile, a periodic, a saltatory, respectively a chaotic event as suggested by some recent studies in animals and in human newborns. Accurate measurements of the lower leg at intervals of 24 hours support the idea of short term growth being characterized by chaotic series of 'mini growth spurts' that occur at intervals of approximately 4-9 days. The amplitude of mini growth spurts ranges between 2 and some 10 mm, and also growth velocity of each spurt varies considerably so that one spurt needs between less than one and up to several days for completion. The very opposite of the variability of individual growth was found in populations. A meta-analysis of 40 male and 51 female European and US American growth studies revealed an almost uniform general pattern of average stature increment during the last 100 years. An additional analysis of stature variation of very large Japanese and Czechoslovakian growth surveys, with all together more than 23000000 measurements, and more than 500000 German preschool and school measurements, suggested similar uniformity in the standard deviation of stature.     

Declining fecundity and ovarian ageing in natural fertility populations

Lower leg length measurements in 19 healthy preterm infants were obtained by knemometry to assess short term growth. Eight infants received fortified human milk and 11 infants commercially available preterm formulas. Two independent observers measured lower leg length in each infant daily during the study period, weight was measured daily with a neonatal scale. While weight gain showed linearity in all infants, lower leg length growth showed mini growth spurts of 5 +/- 1.7 days, growth periods of 20 +/- 11 days or both types of short term growth. The overall weight gain was 35 +/- 5.6 g/day in infants fed human milk and 33 +/- 7 g/day in infants fed preterm formula. The overall lower leg length growth velocity was 0.51 +/- 0.04 mm/day versus 0.54 +/- 0.09 mm/day, respectively. Both groups had comparable weight and length increments. No correlation existed between the type of nonlinear lower leg length growth (mini growth spurts versus growth periods) and the feedings received by the infants.     

Relative importance of growth hormone and sex steroids for the growth at puberty of trunk length, limb length, and muscle width in growth hormone-deficient children

We have followed the growth of stature, sitting height, skinfolds, muscle widths measured radiologically, and skeletal maturity in growth hormone-deficient patients in whom hGH was given and withheld in alternating three-month periods throughout puberty (referred to as "off-hGH" and "on-hGH" periods). Six boys and four girls had true isolated GH deficiency and developed puberty spontaneously. Two boys had gonadotrophin deficiency plus GH deficiency, and five boys had multiple deficiencies; in these boys the signs of puberty were induced by hormone treatment. Boys with true isolated deficiency grew about two-thirds as much in height in the off-hGH periods as in the on-hGH periods; their total gain in height during the adolescent spurt would have been about 20 cm, instead of 30 cm, if hGH had been discontinued at the beginning of puberty. The effect of hGH was entirely on growth in leg-length, however, which virtually ceased during the off-hGH periods. Growth in sitting height altered little when hGH was withdrawn. Growth in limb muscles, however, was GH dependent throughout puberty; during the majority of periods when hGH was withheld, muscle was actually lost; this occurred in the boys who were receiving large doses of testosterone as well as in those producing their own normal amounts. Subcutaneous fat diminished when hGH was given and increased when it was withdrawn; this occurred independently of administration of testosterone. There was little evidence that growth of pubic and axillary hair progressed faster during on-hGH periods, except perhaps in patients with multiple deficiencies. There was some evidence, however, that bone age progressed less rapidly during on-hGH periods than during off-hGH periods in the patients with isolated deficiency. The results in the girls agreed with those in boys so far as stature was concerned, but the relationship with sitting height and leg length appeared to be different; the reasons for this are discussed. We conclude that all children with GH deficiency should continue on treatment with hGH throughout puberty, ideally until growth ceases.     

Subchronic toxicity of a medium-chain chlorinated paraffin in the rat

Groups of ten male and female weanling Sprague-Dawley rats were fed diet containing 0, 5, 50, 500 or 5000 ppm of a medium-chain chlorinated paraffin (C14-17, 52% chlorination) for a period of 13 weeks. Increased relative liver weight was observed at 500 and 5000 ppm in females and at 5000 ppm in males. Relative kidney weight was increased at 5000 ppm in both sexes. Serum cholesterol was increased in the females in a dose-related manner starting at 50 ppm. At 5000 ppm, animals of both sexes had elevated hepatic UDP-glucuronosyltransferase activity while only females showed increased aminopyrine N-demethylase activity. Increased urinary N-acetylglucosaminidase activity occurred at 5000 ppm in females. Increased urinary ascorbic acid excretion monitored at week 12 and a decreased hepatic vitamin A level were detected in females receiving the 500 ppm diet and male and female rats at 5000 ppm. Mild, adaptive histopathological changes were detected in the liver of rats of both sexes at 500 and 5000 ppm, and in the thyroid of males and females starting at 500 and 50 ppm respectively. Minimal changes were observed in the kidney proximal tubules of male rats fed the 5000 ppm diet and in the inner medulla tubules of female rats fed the 500 and 5000 ppm diets. These data indicate that the medium-chain chlorinated paraffin produces biochemical and histological changes at dietary levels of greater than or = 50 ppm in females and greater than or = 500 ppm in males.     

Pairing of Schistosoma mansoni males in infected Syrian hamsters

Pairing of male schistosomes in the liver of infected hamsters was recorded with Egyptians S. mansoni strain. The homospecific male pairs never carried each other in the gynaecophoric duct, but they being closed in either central or hepatic veins. Other perfused males and females en copula showed normal mating behaviour. The paired males were more or less in the same size. The random sexed miracidia used resulted in obtaining 1:2.1 female/male ratio. It is concluded that the random increase of male schistosomes may create the male pairing behaviour. Also, the migration of female against the blood stream to the mesenteric plexus of the host and the failure of male to catch them may lead to this homosexual pairing. The black haemozoin-like substance seen in mature females was also observed in the pairing males and this probably reflects the effect of scarcity or migration of females to the mesenteric plexus.     

TNF-alpha-induced corticosterone elevation but not serum protein or corticosteroid binding globulin reduction is vagally mediated

OBJECTIVE: Growth deficiency is commonly seen in polytransfused beta-thalassaemia patients, especially in adolescence. It is not completely dependent on the lack of their pubertal growth spurt. GH impairment at different levels (hypothalamic or pituitary) and/or a reduced IGF-1 synthesis have been suggested the main causes of stunted growth in these patients. We evaluated the relationship between GH reserve and growth in short beta-thalassaemia patients. PATIENTS: Twenty-nine short patients (height < -1.8 SDS for chronological age) were divided into two groups (low and normal responders) on the basis of their GH peak during insulin and clonidine tests (< or = and > 20 mU/l, respectively). All but one low responders underwent the GHRH test to exclude the impairment of somatotroph function and in eight of them an IGF-1 generation test was also performed. The two groups were compared with each other with respect to growth (height deficiency, height velocity, bone age and bone delay), haematological characteristics (serum ferritin levels, age at the start both of low (subcutaneous) s.c. infusion of desferrioxamine and of transfusional therapy) and serum IGF-1 and IGF-1 binding protein 3 levels. RESULTS: Thirteen patients (45%) (11 males, two females) were low responders, all but two having serum IGF-1 < 5th centile (< 0.1 centile in 42%); the GHRH test excluded the impairment of somatotroph function in 8/12. Height deficiency, serum ferritin levels, and age at the start of s.c. chelating therapy did not differ in low compared to normal responders. Height was negatively correlated both with the age at the start of s.c. chelating therapy and with serum ferritin levels. CONCLUSION: The reduction of GH reserve, more frequently due to a hypothalamic than to a pituitary dysfunction, is frequent in polytransfused beta-thalassaemia patients, especially in males. The height function is not related to the GH reserve, given the current methods for testing GH reserve. Late start of s.c. chelating therapy as well as haemosiderosis seem to play a role in the height deficiency, but not in GH reserve. Impairment of GH secretory reserve, therefore, cannot be considered the main cause of height deficiency in these patients.