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The effect of nutrition on testicular growth in mature Merino rams involves mechanisms that are independent of changes in GnRH pulse frequency.

In mature Merino rams, changes in diet to below or above the requirements for maintenance of body weight lead to changes in gonadotrophin secretion and testicular growth. However, the effects on testicular growth persist for much longer than those on LH and FSH secretion so that the gonadal and gonadotrophin responses are poorly correlated over time. This suggests that the gonadal effects may be partly independent of changes in the hypothalamic secretion of GnRH, an hypothesis tested in this study. In a short-term experiment (November, late spring, non-breeding season), we tested whether a high frequency of exogenous GnRH pulses could override the endogenous system and mimic the change in gonadotrophins seen in rams fed a high plane of nutrition. Mature Merino rams (scrotal circumference (mean +/- S.E.M.) 33.6 +/- 0.5 cm, body weight (mean +/- S.E.M.) 59.0 +/- 0.9 kg) were fed 900 g chaff + 1.6 kg lupin grain (High diet) or 360 g chaff + 60 g lupin grain (Low diet) and infused with 8 pulses of GnRH or saline daily for 5 weeks (n = 5/group). Blood was sampled every 20 min for 12 h on days-1 and 14 relative to the start of treatments. Relative to pre-treatment levels, LH pulse frequency and FSH concentrations were decreased on day 14 in saline-infused rams fed the Low diet and increased in saline-infused rams fed the High diet (P < 0.001). In GnRH-infused rams, gonadotrophin secretion was not affected by diet and the patterns of secretion of LH and FSH were similar to those in saline-infused rams fed the High diet. This model was used for a more complete endocrine analysis in a longer experiment designed to test the hypothesis that the effect of nutrition on testicular growth is partly independent of changes in the secretion of GnRH. The same treatments were imposed for 35 days on a different group of similar rams in March (autumn, mid-breeding season). Body weight and scrotal circumference were measured weekly and blood was sampled on days -1 and 14. On days -1 and 35, testosterone secretion in response to LH was tested by injecting exogenous ovine LH (NIADDK-oLH-25; 200 ng/kg body weight) to all rams. Body weight increased in rams fed the High diet and decreased in those fed the Low diet (P < 0.001) and was not affected by treatments as in experiment 1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Nutritional Physiological Phenomena↗

[Action of gonadotropins on androgen synthesis by embryonic testes of mouse and rat].

Testes from mouse and rat embryos were cultured in vitro in the presence of 14C-sodium acetate and luteinizing hormone or chorionic gonadotrophin. There is an increase in testosterone and androstenedione synthesis from sodium acetate under both treatments. Sensitivity to gonadotrophins exists already at a relatively early stage, when the testis, through testosterone secretion, is building up the genital tract. But the role of the hypophysis in normal androgen secretion will have to be proven.

Acetates↗

A preliminary study of immunological castration in colts.

This study tested the effectiveness of a conjugated GnRH vaccine for stimulating antibody production, suppressing testosterone secretion and depressing testicular development in yearling colts. Two colts were allocated to each of three groups, (1) control, (2) subcutaneous and (3) intramuscular vaccinations. Two injections of the vaccine were given 11 weeks apart. Liveweight gain was not affected by vaccination but plasma testosterone concentrations in the treated colts were suppressed and their antibody titres to GnRH were greater than 1:1000. Testicular development in the treated colts also was retarded at this time, which was approximately 28 weeks after the first injection. Semen samples, containing spermatozoa, were collected from all the colts prior to their castration at the end of the investigation. Antibody titres and testosterone concentrations in the treated colts had returned to levels similar to those of the controls by the end of the experiment. The testes of the vaccinated colts were still smaller than those of the controls on castration but were, nevertheless, increasing in size. Morphometric analysis of testicular histology and daily sperm production data indicated that the testes of the treated colts were recovering and would probably have regained normal function had they been left in situ.

Animals↗

Oxandrolone induces a sustained rise in physiological growth hormone secretion in boys with constitutional delay of growth and puberty.

We describe the treatment of 3 boys, mean age 14.9 years (range 13.8-16.1 years) with constitutional delay of growth and puberty using oxandrolone in two dose regimens, 2.5 or 1.25 mg/day for 3 months. Treatment induced an increase in mean height velocity from 5.1 to 8.5 cm/year; this was sustained at 8.8 cm/year in the period following treatment. Growth hormone (GH), luteinising hormone and testosterone secretion were assessed by overnight or 24-hour venous sampling at 15-min intervals before, during treatment and after cessation of treatment. A computer programme was used to analyse GH secretory dynamics. The 3 boys had a mean sustained increase in total GH secretion of 190%. The increase in GH secretion was associated with an increase in amplitude of GH pulses rather than an alteration in pulse frequency.

Adolescent↗

The challenge hypothesis and seasonal changes in aggression and steroids in male northern fence lizards (Sceloporus undulatus hyacinthinus).

The challenge hypothesis has been very successful in explaining patterns of testosterone secretion in response to social stimuli in avian species. However, there have been few studies in nonavian vertebrates. We tested the challenge hypothesis in male northern fence lizards (Sceloporus undulatus hyacinthinus). These males are highly territorial and nonparental. Consequently, the challenge hypothesis predicts that plasma testosterone concentrations will be insensitive to aggressive interactions. Testosterone concentrations indeed were not significantly affected by either a short (3-15 min) simulated territorial intrusion ("challenge") in June or a longer (50-60 min) intrusion in July. Levels of corticosterone were elevated in challenged males in the long, but not the short, intrusion. Challenged males displayed significantly more intense territorial behaviors than did unchallenged control males. The intensity of territorial behavior changed significantly across the active season and was positively related to testosterone concentrations. Thus, while testosterone concentrations do not appear to be involved in rapid changes in aggressive behavior in the fence lizard, they probably are important in larger-scale behavioral changes throughout the season.

Aggression↗

Changes in the concentrations of testosterone and androstenedione in the plasma and testis of the guinea-pig from birth to death.

Testosterone and androstenedione concentrations in the plasma and testis of male guinea-pigs were estimated by gas chromatography at intervals (36 stages) from birth to death. Four main periods of androgenic activity were recognized. The neonatal period, from birth to Day 16, is characterized by a precocious but transient peak in plasma testosterone concentration at Days 2 and 3. The pubertal period from Days 16 to 90 can be subdivided into a prepubertal period starting on Day 16 and marked by a sudden linear increase in plasma and testicular testosterone concentration together with an increase in testicular and seminal vesicle weight, and a postpubertal period, from Day 50 (the time of hormonal puberty) to Day 90, characterized by high and stable androgen levels while testicular and genital tract development continues. Adulthood spans the period between Months 3-6 and Month 24; plasma and testicular concentrations of testosterone and androstenedione are stable but lower than those observed during puberty. The period of senescence occurs between Months 24 and 28 and is marked by a fall in testosterone secretion and involution of the seminiferous tubules and accessory sex glands.

Aging↗

The aging male: androgens, erectile dysfunction, and depression.

In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, there is a progressive reduction in hypothalamic-pituitary-gonadal (HPG) axis activity in aging men: testosterone levels decline and there is a loss of the circadian rhythm of testosterone secretion. Such progressive HPG-axis hypofunctioning is thought to be responsible for some signs and symptoms that are common in elderly men such as fatigue, reduced muscle and bone mass, sexual dysfunction, and depression. Yet, such presumed hypogonadal sequelae have not been correlated with testosterone levels. Unlike the profound effects of replacement therapy in young men with frank hypogonadism, testosterone replacement in men with age-related mild hypogonadism is not apparently effective in reversing these symptoms. This article reviews the relationship between androgens, sexual function, and depression in aging men.

Adult↗

[Histogenesis on the ovarian Leydig cell tumor--light microscopic dry-mounting radioautography for 3H-cholesterol and electron microscopic cytochemistry for 3 beta-hydroxysteroid dehydrogenase activity].

A case of a virilizing ovarian Leydig cell tumor in a 38 year-old woman with a markedly elevated plasma testosterone level was investigated using light microscopic dry-mounting radioautography and electron microscopic cytochemistry. Following total abdominal hysterectomy and bilateral salpingo-oophorectomy, the plasma testosterone level fell abruptly. Light microscopic dry-mounting radioautography for 3H-cholesterol showed silver grains mainly localized over the cytoplasm of the tumor cells. In the Leydig cell tumor there were three different cell types: Fibroblast-like cells, Leydig cells (steroid-secreting cells) and transitional cells (partially or incompletely differentiated Leydig cells). Reaction products for 3 beta-hydroxysteroid dehydrogenase activity were localized on tubular or lamellar cristae and inner membranes of the mitochondria, and on the membranes of smooth endoplasmic reticulum in the transitional cell as well as in the Leydig cell. From these facts, it is suggested that the Leydig cell tumor is derived from the fibroblast-like cell and the Leydig cell, already has a steroidogenic activity in secreting testosterone.

3-Hydroxysteroid Dehydrogenases↗

Modulation of testicular functions by testicular opioid peptides.

The possible physiological role of testicular opioid peptides in the control of testicular functions has been studied. In neonatal rats intratesticular administration of opiate receptor antagonists (naloxone, nalmefene) stimulates Sertoli cell proliferation and secretion. Both in adult and neonatal rats local injection of the testis with opiate receptor antagonists or with beta-endorphin antiserum results in a decrease in steroidogenesis in long-term studies. Treatment of neonatal testis with an enkephalin analogue induces a short-term suppression of testosterone secretion. Further studies were carried out to investigate whether the above described local effects of opiate agonist or antagonist on testicular function are under the regulatory control of testicular nerves. Partial denervation of the testis was performed by testicular injection of 6-hydroxydopamine (a neurotoxin degenerating sympathetic neural structures) or by vasectomy (cutting the inferior spermatic nerve). If testicular administration of opioid agonist or antagonist was combined with partial denervation of the testis, the effects of pharmacological agents influencing testicular opioid level were not evident. The data indicate that opioid peptides synthesized in the testis are components of the intratesticular regulatory system and that local opioid actions are modulated by testicular nerves.

Animals↗

Effect of follicular steroids on the maturation and fertilization of mammalian oocytes.

Pronuclear development was used to measure the effects on ovine oocytes of altering follicular steroidogenesis during maturation in vitro. Follicular steroid secretion was altered using enzyme inhibitors and exogenous steroid supplementation. Abnormalities induced during maturation were measured 24 h after tranfer of oocytes to the oviducts of inseminated hosts. The presence throughout maturation of aminoglutethimide, an inhibitor of the conversion of cholesterol to pregnenolone, reduced steroid secretion to 7% of that in controls and decreased from 77% to 33% the number of normal oocytes. Abnormalities were substantially reduced by the addition of aminoglutethimide during the final 8 h of maturation only. The inhibition of 17 alpha-hydroxylase enzymes with SU10603 reduced oestrogen and testosterone secretion to about 10% of control levels but had no effect on progestin secretion. Only 13% of oocytes matured in the continual presence of SU10603 underwent normal fertilization. The number of oocytes undergoing normal fertilization was increased to about 50% by (i) delaying the addition of SU10603 until the last 8 h of the maturation period or (ii) adding exogenous steroids to follicles cultured with inhibitor from explantation. It is concluded that oocytes require a specific intra-follicular steroid environment for the completion of the full maturation process. Alterations to the steroid profile during maturation induce changes in the oocyte which are expressed as gross abnormalities at fertilization.

Aminoglutethimide↗

Effect of pineal gland on testosterone release in vitro.

We studied the effect of hCG, aminoglutethimide and pineal effluent on the basal testosterone secretion by superfused adult rat interstitial cells. The period used to determine the mean rates of release was 120-240 min. after the start of superfusion i.e. when basal secretory rate was stable. A 2 h administration of hCG (10 mUI/ml) induced a rapid increase in testosterone output while aminoglutethimide (100 microM) decreased it. Basal testosterone release was not modified when interstitial cells were superfused with effluent of a chamber containing 1, 2 or 4 pineal glands. These results suggest that pineal secretory products exert no direct acute action on testosterone biosynthesis by rat interstitial cells.

Aminoglutethimide↗

Developmental changes and differential regulation by testosterone and estradiol of growth hormone receptor expression in the rabbit.

To investigate the effects of testosterone and estradiol (E2) on growth hormone receptor (GH-R) gene expression, we measured GH-R mRNA levels in relation to the changes of sex steroid concentrations in the normal male rabbits aged 1-12 months and after administration of testosterone or E2 to castrated male rabbits. In the normal animals, E2 levels were below the detection limit in all age groups, and testosterone levels were below the detection limit at 1 month, increased at 2 months and reached the plateau of the adult levels after 4 months. Liver GH-R mRNA levels were low at 1 month, reached a peak at 2 months and then decreased slightly thereafter. In the castrated animals, liver and growth plate GH-R mRNA levels were increased in the testosterone-treated group (162.0 +/- 12.0%, p < 0.025; 128.4 +/- 7.6%; p < 0.025) and reduced in the E2-treated group (29.6 +/- 6.2%, p < 0.005; 53.6 +/- 11.3%, p < 0.025). Sex steroid administration did not result in any significant change in GH-R mRNA levels in striated muscle, kidney and heart. Serum GH concentrations were increased in E2 (15.3 +/- 7.7 microg/l vs 4.8 +/- 2.2 microg/l, p < 0.025) but the increase was not significant in testosterone-treated animals (8.4 +/- 7.7 microg/l vs 4.8 +/- 2.2 microg/l). Both testosterone and E2 treatment resulted in a reduction of mean serum growth hormone-binding protein (GHBP) levels compared to control animals (1077 +/- 422 pmol/l, p < 0.01; 1137 +/- 443 pmol/l, p < 0.01; 2308 +/- 565 pmol/l). We conclude that in addition to their stimulatory effect on GH secretion, testosterone and E2 have opposite effects on GH-R gene expression in liver and growth plate in the rabbit. The modulation of GH-R expression by sex steroids may be important for growth during sexual maturation in mammals.

Aging↗

Developmental changes in gonadotrophins and testicular gonadotrophin receptors in the pig, from neonatal to adult life.

Changes in the concentrations of LH and FSH testicular receptors have been studied in the pig, from neonatal to adult life, and correlated with blood LH, FSH and testosterone concentrations. Quantification of gonadotrophin receptors was performed in equilibrium binding studies, using homologous systems. The presence of high-affinity binding sites for LH and FSH (association constant (Ka): LH approximately 20 litres/nmol; FSH approximately 10 litres/nmol) was demonstrated in the testes of all animals studied. The apparent affinity of LH and FSH receptors did not change significantly with age. During the first weeks of life, there was a transient rise in LH receptor content, reaching a maximum of 8.7 +/- 2.2 (mean +/- S.E.M.) pmol/g testis at 24 days of age. This was correlated with a peak in testosterone secretion and reflects the second wave of interstitial cell proliferation in the pig. A second increase in the number of LH receptors occurred after 12 weeks of age and corresponds to pubertal maturation and final differentiation of adult Leydig cells. During this period, circulating concentrations of testosterone markedly increased without any significant variation in LH blood levels, suggesting a change in testicular sensitivity to LH in the maturing pig. A continuous increase in FSH receptor content was observed from the neonatal to the adult pig. This increase occurred in two phases. During the first 2 months of life, the increase in the number of FSH receptors exceeded that of testis growth rate and resulted in an increase in FSH receptor concentrations which reached a peak at 12.1 +/- 1.8 pmol/g testis, at week 9.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Circulating inhibin alpha concentrations in infant, prepubertal, and adult male rhesus monkeys (Macaca mulatta) and in juvenile males during premature initiation of puberty with pulsatile gonadotropin-releasing hormone treatment.

Circulating inhibin alpha concentrations were determined in infant, juvenile, and adult male rhesus monkeys with a RIA employing antisera to a synthetic fragment of the alpha-subunit of porcine inhibin. Binding of tracer, [DSer1,Nle5]human inhibin alpha(1-25)-Gly-125I-Tyr, to antibody was inhibited by standard, [DSer1,Nle5]human inhibin alpha(1-25)-Gly-Tyr. and by plasma from adult male monkeys in a parallel fashion. Castration in adults resulted in a 5-fold decline in the levels of immunoreactivity in plasma. Mean (+/- SE) plasma inhibin alpha concentrations in infants and adults (322.9 +/- 51.9 and 460.1 +/- 43.9 pg/ml, respectively) were significantly higher (P less than 0.05) than those in juveniles (191.3 +/- 28.3 pg/ml). Moreover, initiation of puberty in juvenile males, 13-18 months of age, with a chronic (10- to 12-week) intermittent iv infusion of GnRH (0.1 microgram/min for 3 min every 3 h) resulted in a progressive rise in circulating inhibin alpha that plateaued, after 5 weeks of pituitary stimulation, at concentrations (343.9 +/- 38.2 pg/ml) comparable to those of infants and adults and twice those observed before initiation of the pulsatile infusion of GnRH. Circulating FSH concentrations increased during the first week of GnRH stimulation from 2.7 +/- 0.1 ng/ml before treatment to 6.0 +/- 1.2 ng/ml, where they remained for the duration of the experiment. Testosterone secretion during the initiation of precocious puberty occurred in discrete episodes that were robustly correlated with GnRH-induced LH discharges. In contrast, changes in circulating inhibin alpha concentrations over the 3-h interval between GnRH pulses were unremarkable. Activation of Sertoli and Leydig cells during initiation of puberty in the juvenile males, as reflected by circulating inhibin alpha and testosterone concentrations, respectively, occurred with similar time courses. At the time of orchidectomy, 10-12 weeks after initiation of GnRH treatment, testicular tissue was prepared for histological examination. In spite of a 2-fold gain in testicular weight and in hypertrophy of Sertoli cells in association with GnRH stimulation, maturation of the germinal epithelium did not progress past prophase I spermatocytes, and the number of these latter cells was meager. These findings indicate that the testis of the infant primate, like that of the adult, secretes significant amounts of inhibin, and that the quiescent Sertoli cell of the juvenile males may be readily provoked by appropriate gonadotropin stimulation into producing inhibin. The results also fail to provide evidence for the view that changes in circulating inhibin concentrations are robustly related, in an inve

Aging↗

Effect of continual light deprivation and alpha-2u-globulin replacement therapy on serum concentration of gonadotropins and testicular activity in rats.

Prolonged darkness caused a fall in testicular 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity and diminished spermatogenesis, serum levels of gonadotropins, testosterone and alpha 2u-globulin. Administration of alpha 2u-globulin at a dose of 1.5 mg rat-1 per day for 7 days after 68 days of light deprivation, reversed the 17 beta-HSD activity and serum levels of gonadotropins, testosterone and alpha 2u-globulin, while spermatogenesis was restored to normal. The animals kept in prolonged darkness for 68 days and then received saline (7 days in light-dark cycle, 14 L: 10 D), showed no significant changes of testicular activity, serum levels of gonadotropins, testosterone and alpha 2u-globulin, when compared with dark-exposed animals (68 days) receiving rabbit serum (7 days in light-dark cycle, 14 L: 10 D). These results suggest that alpha 2u-globulin plays an important role in testicular function in dark-exposed rats by inducing gonadotropins and testosterone secretion.

Alpha-Globulins↗

Effects of melatonin implants on plasma concentrations of testosterone, thyroxine and prolactin in the male silver fox (Vulpes vulpes).

Melatonin administration in the form of slow-release implants advanced breeding activity in silver fox males when treatment began in June. Plasma testosterone concentrations were significantly higher in treated animals than in controls from September to November, whereas in February and March they were significantly lower. Plasma prolactin concentrations were significantly reduced immediately following melatonin treatment in June but increased to greater levels than control values and 'peaked' after 7 months. This 'peak' was associated with a rapid decrease in testosterone secretion. The normal seasonal spring rise in prolactin secretion was prevented by melatonin administration. Thyroxine values decreased and were significantly lower after 2 months of melatonin treatment.

Animals↗

[Clinical, cytogenetical, histological, immunological and hormonal studies in a case of true hermaphroditism (author's transl)].

A true hermaphrodite with ambiguous genitalia and 46 XX caryotype was investigated during adolescence. At 13 years testosterone concentrations (ng/ml) were 6 and 390 respectively in peripheral and right ovotestis venous blood. After removal of the right gonad, large fluctuations of estradiol levels (40 to 220 pg/ml) were observed. But the testosterone secretion by the left ovotestis was low, although responsive to hCG. A significant LH surge was induced by ethinyl-estradiol load before removal of the left gonad. The 5 alpha-reductase activity was normal in the pubic skin and the levels of cytosolic receptors of testosterone and DHT were high in the left gonad. The presence of H-Y antigen was demonstrated on lymphocytes.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Intratesticular hormone levels and the route of secretion of hormones from the testis of the rat, guinea pig, monkey and human.

Blood samples were obtained from the testes of rats, guinea pigs and Macaque monkeys and from normal men undergoing vasectomy reversal, in order to assess the comparative dynamics of hormone secretion. In each species, blood was sampled from a vein on the surface of the testis (testicular venous blood, TV), from a vein in the spermatic cord above the pampiniform plexus (spermatic venous blood, SV) and from a vein elsewhere in the body (peripheral venous blood, PV). Plasma concentrations of testosterone and inhibin were then determined by radioimmunoassay. In all species, testosterone secretion profiles were comparable, with concentrations being greatest in TV blood. SV concentrations were reduced by 40-60% compared with TV levels, with a significantly greater reduction in PV levels. Inhibin secretion varied significantly between species, with the rat being the only animal to show significant increases in inhibin concentrations from TV to SV blood. Inhibin secretion in the guinea pig was most comparable with that of the rat, although the increased SV levels fell short of being significant. Macaque and human profiles contrasted with those of the rat and guinea pig, with the greatest inhibin concentrations being found in TV blood. Levels in SV blood were reduced by some 40%, and PV levels were reduced significantly further. These differences may be due to the different position of the rete testis, and its relationship to the testicular vasculature, in these species. The sampling procedure described provides a defined set of testicular blood samples that could contribute important information of relevance to physiological and clinical studies of testicular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗