Effects of exogenous testosterone on testicular luteinizing hormone and follicle-stimulating hormone receptors during aging

During aging, the male Japanese quail exhibits a loss of fertility, increased morphological abnormalities in the testes, and a higher incidence of Sertoli cell tumors. Although there is a coincident loss of reproductive behavior, plasma androgen levels remain high until testicular regression occurs in association with senescence. The purpose of this study was to compare mean specific binding of chicken luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as a measure of testicular receptors during identified stages during aging. Males were categorized according to age (young = 9 months, middle aged = 24 months, or old = 36+ months) and sexual behavior (active or inactive). Testicular samples were collected immediately after perfusion with 4% paraformaldehyde from the following groups: young active (n = 8), young photoregressed (n = 5), young photoregressed plus testosterone implant (n = 4), middle-aged active (n = 8), middle-aged inactive (n = 4), old inactive (n = 5), and old inactive plus testosterone implant (n = 6). A crude plasma membrane fraction was prepared from the testes of each bird and an aliquot deriving from 10 mg of testicular tissue was used for binding assay. Specific binding of labeled LH or FSH was expressed as percentage of total radioactive hormone. Results showed significant (P < 0.05) age-related decreases in both FSH and LH receptor numbers. The highest FSH binding was found in young and middle-aged active males, with low binding in old inactive males. Testicular LH binding decreased during aging, with a sharp decrease in middle-aged males, which was similar to old males. Testosterone implants weakly stimulated FSH and LH binding in old males. Both LH and FSH binding decreased in photoregressed young males. However, testosterone implants stimulated increased LH binding, but did not affect FSH binding in young photoregressed males. These results provide evidence for separate regulation of testicular LH and FSH receptors, with testosterone stimulation of LH receptor, but not FSH receptor number in young males. However, during aging there appears to be a loss of this response, potentially because of the reduced efficacy of testosterone stimulation, thereby implying a diminished capacity for response with aging.     

Restoration of normal gonadotropin responses to naloxone by chronic bromocriptine treatment in elderly men.

Naloxone is unable to stimulate FSH and LH secretion in elderly men, suggesting a reduced endogenous opioid control of gonadotropin secretion in senescence. In the present study, we examined whether in elderly men a chronic dopaminergic stimulation with bromocriptine (5 mg/day for 7 days) modifies the gonadotropin response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 h). Eleven younger men (group 1, 22-40 years old) participated as controls. Twenty-two elderly men were selected from a larger population and were divided into two groups: subjects with compensated gonadal failure (normal blood testosterone and elevated gonadotropin concentrations; group 2, n = 11; 62-80 years old) and men with normal gonadal function (normal blood testosterone and gonadotropin levels; group 3, n = 11; 61-82 years old). Naloxone induced a striking LH and a slight but significant FSH increase in group 1, but was unable to change serum gonadotropin concentrations in elderly subjects of both groups 2 and 3. When experiments were repeated after bromocriptine treatment, no significant differences in LH and FSH responses to naloxone were observed in the younger subjects. On the other hand, bromocriptine restored significant gonadotropin responses to naloxone in elderly men. In fact, after bromocriptine, naloxone-induced FSH and LH increments in groups 2 and 3 were indistinguishable from those observed in group 1. These data suggest that in men age-related dopaminergic alterations may underlie the defective endogenous opioid control of gonadotropin secretion.     

Endocrine alterations and signaling changes associated with declining ovarian function and advanced biological aging in follicle-stimulating hormone receptor haploinsufficient mice

Reproductive aging in female mammals is characterized by a progressive decline in fertility due to loss of follicles and reduced ovarian steroidogenesis. In this study we examined some of the endocrine and signaling parameters that might contribute to a decrease in ovulation and reproductive performance of mice with haploinsufficiency of the FSH receptor (FSH-R). For this purpose we compared ovarian changes and hormone levels in FSH-R heterozygous (+/-) and wild-type mice of different ages (3, 7, and 12 mo). Hormone-induced ovulations in immature and 3-mo-old +/- mice were consistently lower. The number of corpora lutea (CL) were lower at 3 and 7 mo, and none were present in 1-yr-old +/- females. The plasma steroid and gonadotropin levels exhibited changes associated with typical ovarian aging. Plasma FSH and LH levels were higher in 7-mo-old +/- mice, but FSH levels continued to rise in both genotypes by 1 yr. Serum estradiol and progesterone were lower in +/- mice at all ages, and testosterone was several-fold higher in 7-mo-old and 1-yr-old +/- mice. Inhibin alpha (Western blot) appeared to be lower in +/- ovaries at all ages. FSH-R (FSH* binding) declined steadily from 3 mo and reaching the lowest point at 1 yr. LH receptor (LH* binding) was high in the 1-yr-old ovary, and expression was localized in the stroma and interstitial cells. Our findings demonstrate that haploinsufficiency of the FSH-R gene could cause premature exhaustion of the gonadal reserves previously noted in these mice. This is accompanied by age-related changes in the hypothalamic-pituitary axis. As these features in our FSH-R +/- mice resemble reproductive failure occurring in middle-age women, further studies in this model might provide useful insights into the mechanisms underlying ovarian aging.     

Relationship between adenohypophyseal and steroid hormones and variations in serum and urinary melatonin levels during the ovarian cycle, perimenopause and menopause in healthy women

Morning levels of serum melatonin, FSH, LH, prolactin (PRL), progesterone and estradiol were studied by RIA during the ovarian cycle, perimenopause and menopause in 79 healthy women. FSH and LH levels showed a slight nonsignificant increase from the fertile period to perimenopause, exhibiting a significantly greater increase during menopause. PRL, progesterone and estradiol showed parallel changes, reaching lower levels during menopause. Serum melatonin levels decreased with age, attaining minimum levels in menopause. FSH and estradiol were significantly correlated with melatonin in the follicular phase, while in the luteal phase a negative correlation was found between melatonin, progesterone and estradiol. No significant correlations were noted between serum hormone levels during the perimenopausal period. In menopause, as during the follicular phase, melatonin and FSH were negatively correlated. As expected, a significant positive correlation was found between morning serum levels of melatonin and nocturnal urinary excretion of this indoleamine in all groups studied.     

Regulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) gene expression by gonadotropin-releasing hormone (GnRH) and sexual steroids in the Mediterranean Sea bass

The secretion of gonadotropins, the key reproductive hormones in vertebrates, is controlled from the brain by the gonadotropin-releasing hormone (GnRH), but also by complex steroid feedback mechanisms. In this study, after the recent cloning of the three gonadotropin subunits of sea bass (Dicentrarchus labrax), we aimed at investigating the effects of GnRH and sexual steroids on pituitary gonadotropin mRNA levels, in this valuable aquaculture fish species. Implantation of sea bass, in the period of sexual resting, for 12 days with estradiol (E2), testosterone (T) or the non-aromatizable androgen dihydrotestosterone (DHT), almost suppressed basal expression of FSHbeta (four to 15-fold inhibition from control levels), while slightly increasing that of alpha (1.5-fold) and LHbeta (approx. twofold) subunits. Further injection with a GnRH analogue (15 microg/kg BW; [D-Ala6, Pro9-Net]-mGnRH), had no effect on FSHbeta mRNA levels, but stimulated (twofold) pituitary alpha and LHbeta mRNA levels in sham- and T-implanted fish, and slightly in E2- and DHT-implanted fish (approx. 1.5-fold). The GnRHa injection, as expected, elevated plasma LH levels with a parallel decrease on LH pituitary content, with no differences between implanted fish. In conclusion, high circulating steroid levels seems to exert different action on gonadotropin secretion, inhibiting FSH while stimulating LH synthesis. In these experimental conditions, the GnRHa stimulate LH synthesis and release, but have no effect on FSH synthesis.     

Bovine model for the study of reproductive aging in women: follicular, luteal, and endocrine characteristics

At present, there is no well-characterized animal model to study the effects of aging on fertility in women. The objectives of the study were to characterize age-related changes in ovarian and endocrine functions in old cows and to investigate the validity of a bovine model for the study of human reproductive aging. We tested the hypotheses that aging in cattle is associated with 1) elevated concentrations of gonadotropins and reduced concentrations of steroid hormones in systemic circulation and 2) increased recruitment of ovarian follicles during wave emergence. Daily ultrasonography was performed in 13- to 14-yr-old cows (n = 10) and their 1- to 4-yr-old daughters (n = 9) for one interovulatory interval to study ovarian function. Plasma samples were obtained every 12 h for determination of FSH, LH, progesterone, and estradiol concentrations. Circulating FSH concentrations were higher (P = 0.009) during follicular waves in old cows than in their daughters, but the number of 4- to 5-mm follicles recruited into a wave was lower (P = 0.04) in old cows. Plasma LH concentrations did not differ between groups (P = 0.4), but the ovulatory follicle in two-wave cycles was smaller in old cows (P = 0.04). Plasma estradiol concentrations were higher (P = 0.01) in old cows, and luteal phase progesterone tended to be lower (P = 0.1). We conclude that these changes are consistent with those reported for women approaching menopause transition. Therefore, our results validate the use of the bovine model to study reproductive aging in women.     

Different effects of aging on the opioid mechanisms controlling gonadotropin and cortisol secretion in man

The present study was undertaken in order to assess the influence of aging on the endogenous opioid control of gonadotropin and adrenocorticotropin/cortisol secretion in man. For this purpose, the capability of the opioid antagonist naloxone to increase circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol was tested in male subjects of different ages. Thirty normal men were randomly chosen and divided into 3 groups by age: group I = 22-40 years (n = 10); group II = 41-59 years (n = 10); group III = 62-80 years (n = 10). Since the men of group III showed higher basal serum gonadotropin concentrations than the subjects of group I and group II, we selected from a large population a fourth group of elderly men with normal basal LH and FSH levels: group IV = 61-82 years (n = 7). All subjects were tested for 120 min during the intravenous administration of naloxone (4 mg given in an intravenous bolus at time 0, plus 10 mg infused for 2 h). Control tests with normal saline instead of naloxone were performed in all groups. All subjects had similar blood testosterone and cortisol levels, whereas LH and FSH concentrations were significantly higher in group III than in groups I, II and IV. Naloxone increased plasma cortisol concentrations by 50% in all groups. The cortisol secretory response followed a similar pattern regardless of age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Steroidal modulation of in vitro gonadotropin secretion in prepubertal and adult male Siberian hamsters

The effects of exogenous gonadal steroids, testosterone (T), and 17beta-estradiol (E(2)) upon the hypothalamo-pituitary-gonadal axis were reported to be different between prepubertal and adult Siberian hamsters. Utilizing an in vitro static culture system, we investigated if age-related differences in steroid responsiveness occurs at the pituitary. Prepubertal (20 days old) or adult (140 days old) male Siberian hamsters were implanted with 1 mm silastic capsules containing undiluted T, E(2) or cholesterol (Ch, control). After 15 days, pituitaries were removed, incubated in vitro, and subjected to the following treatments: two baseline measurements, one challenge with 10ng/ml of D-Lys(6)-gonadotropin-releasing hormone (GnRH), and three post-challenge washes. Fractions were collected every 30 minutes and measured for follicle-stimulating hormone (FSH) and luteinizing hormone (LH). T and E(2 )reduced basal secretion of LH and FSH in juveniles but not adults. In juveniles, E(2) increased GnRH-induced FSH and LH secretion, while T augmented GnRH-induced FSH secretion but attenuated GnRH-induced LH secretion. Steroid treatment had no effect on GnRH-stimulated LH or FSH release in adults. The only effect of steroid hormones upon adult pituitaries was the more rapid return of gonadotropin secretion to baseline levels following a GnRH challenge. These data suggest both basal and GnRH-induced gonadotropin secretion are more sensitive to steroid treatment in juvenile hamsters than adults. Further, differential steroidal regulation of FSH and LH at the level of the pituitary in juveniles might be a mechanism for the change in sensitivity to the negative effects of steroid hormones that occurs during the pubertal transition.     

Plasma and pituitary concentrations of gonadotropins (FSH and LH) in minke whales (Balaenoptera acutorostrata) during the feeding season

This study investigated plasma and pituitary concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and steroid hormones (progesterone: P4, testosterone:T, estradiol-17beta: E2) by enzyme-immunoassay (EIA) in minke whales (Balaenoptera acutorostrata) captured during the feeding season (December to March) in the Antarctic Ocean. Plasma FSH and LH levels in female minke whales were higher (P <0.05) than in male whales. Although the pituitary weight was not significantly different between male and female whales, pituitary FSH and LH levels were higher in females than in males (P<0.01) and mature whales than immature whales (P<0.05). Plasma levels of FSH, T and E2 were not significantly different between immature and mature male whales, but plasma LH and pituitary FSH and LH levels were higher (P<0.05) in mature than in immature whales. In both immature and mature whales regardless of gender, pituitary FSH and LH levels were correlated significantly (r=0.69: P<0.01). In mature male whales, plasma T and E2 levels (r=0.60: P<0.01), and testis weight and plasma T levels (r=0.46: P <0.05) were correlated. In immature female whales, plasma FSH and LH levels were highly correlated (r=0.68: P<0.001), but were not for mature female whales. The results show that gender and maturity influence gonadal and pituitary function of minke whales during the feeding season.     

Androgens positively regulate follicle-stimulating hormone beta-subunit mRNA levels in rat pituitary cells

We have shown previously that androgens negatively regulate LH alpha and beta-subunit mRNA levels, but have little or no effect on FSH beta mRNA levels in rats in vivo. In contrast, estrogen negatively regulates all three gonadotropin subunit mRNA levels in vivo. We have examined the effects of these sex steroids on gonadotropin subunit synthesis directly at the level of the pituitary gland by using cultured rat pituitary cells. Adult female and male rat pituitaries were dissected, dispersed enzymatically, and maintained in culture for 2 days. At that time, cells were treated for varying lengths of time with either medium alone or sex-steroid hormone treatments (estradiol or testosterone). Dose-response and time-course experiments were performed. Cells were then harvested and total RNA was extracted. Gonadotropin subunit mRNA levels were assessed by blot hybridization techniques. Sex-steroid hormones were added to achieve final concentrations ranging from 10(-12) to 10(-6) M for dose response experiments and 10(-8) M for time-course experiments. Testosterone treatment (10(-8) M) increased FSH beta mRNA levels 3-fold in females (P less than 0.01) and males (P less than 0.05), but had no effect on alpha or LH beta mRNA levels in either sex. Dose-related increases in FSH beta mRNA levels with increasing concentrations of testosterone were observed in both female and male pituitary cell cultures. Time-course studies revealed that the testosterone-stimulated increases in FSH beta mRNA levels are statistically significant by 12 h and 6 h after hormone addition in female and male cultures, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reproductive hormone profiles in captive male orangutans: Implications for understanding developmental arrest

For many years researchers have described some male orangutans as “subadult.” These males are of adolescent to adult age and are reproductive, but have little to no secondary sexual trait development. Until now the only endocrine study of this arrest of secondary sexual trait development was performed by Kingsley (1982, 1988). She found that “subadult” or arrested males have lower testosterone levels than similar age developing adolescents or adult males. In this study, urine samples were collected over a two-year period from 23 captive male orangutans in order to more fully define male endocrine profiles. Three study males were juveniles, seven were arrested adolescents, six were developing adolescents, and seven were mature adults. Morning samples were analyzed by radioimmunoassay for levels of testicular steroids and gonadotropins and group hormone profiles were compared by analysis of variance. Results illustrate that arrested adolescent orangutans have significantly lower testosterone and dihydrotestosterone (DHT) levels than developing adolescents, but significantly higher levels than juveniles. Luteinizing hormone (LH) levels also differed between arrested and developing adolescents, with arrested males having lower levels. However, follicle stimulating hormone (FSH) levels were similar in both morphs of adolescent male. The overall hormone profiles for arrested and developing adolescent male orangutans suggest that arrested males lack levels of LH, testosterone, and DHT necessary for development of secondary sexual traits. However, they have sufficient testicular steroids, LH, and FSH to fully develop primary sexual function and fertility. These endocrine data help define alternative developmental pathways in male orangutans. The authors discuss the relationship between these developmental pathways and male orangutan reproductive strategies, and hypothesize about their prepubertal socioendocrine determination. Am J Phys Anthropol 109:19–32, 1999. © 1999 Wiley-Liss, Inc.     

Divergent regulation of gonadotropin subunit mRNA levels by androgens in the female rat.

To examine the effects of gonadal steroids on the pretranslational regulation of the gonadotropin subunits in the female, adult female rats, beginning 7 or 28 days after ovariectomy, received daily injections of testosterone propionate (T), dihydrotestosterone propionate (D), or estradiol benzoate (E) for 7 days. Intact cycling females and ovariectomized rats that received vehicle served as controls. Serum was obtained for LH and FSH levels to assess changes in gonadotropin secretion. Total RNA from individual rats was recovered and analyzed by blot hybridization with specific radiolabeled cDNA probes for the alpha, LH beta, and FSH beta subunits. Autoradiographic bands were quantitated and standardized to mRNA levels in the intact animals. Ovariectomy resulted in a rise in serum gonadotropin levels and all three gonadotropin subunit mRNA levels. Estrogen replacement resulted in suppression of alpha, LH beta, and FSH beta mRNAs whether given at 7 or 28 days after ovariectomy. In contrast, whereas androgen replacement decreased alpha and LH beta mRNAs, D or T did not consistently suppress FSH beta mRNAs. We conclude that chronic estrogen administration to the castrated female rat uniformly suppresses all three gonadotropin subunit mRNA levels. In female rats, as in male rats, chronic androgen administration fails to negatively regulate FSH beta mRNAs.     

Inhibin B,follicle stimulating hormone,luteinizing hormone,and estradiol and their relationship to the regulation of follicle development in girls during childhood and puberty

Inhibin B, produced by granulosa cells in the ovary, is a heterodimeric glycoprotein suppressing synthesis and secretion of the follicle stimulating hormone (FSH). The aim of the present study was to determine hormone profiles of inhibin B, FSH, luteinizing hormone (LH), and estradiol in girls during childhood and puberty and to evaluate whether inhibin B is a marker of follicle development. We examined the correlation between inhibin B and gonadotropins and estradiol during the first two years and across the pubertal development. Using a specific two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels were measured in the serum of 53 healthy girls divided into 8 groups according to age. In addition, serum FSH, LH, and estradiol were measured by chemiluminescent immunoassay in all serum samples. A rise in serum levels of inhibin B (55.2+/-7.3 ng/l, mean +/- S.E.M.) and FSH (1.78+/-0.26 UI/l), concomitant with a moderate increment of serum LH (0.36+/-0.09 UI/l) and estradiol (45.8+/-12.2 pmol/l) concentrations was observed during the first three months of life and declined to prepubertal concentrations thereafter. A strong positive correlation between inhibin B and FSH (r = 0.48, p<0.05), LH (r = 0.68, p<0.001) and estradiol (r = 0.59, p<0.01) was demonstrated during the first 2 years of life. A rise in serum levels of inhibin B, FSH, LH, and estradiol was found throughout puberty. Inhibin B had a strong positive correlation with FSH (stage I of puberty: r = 0.64, p<0.05; stage II of puberty: r = 0.86, p<0.01), LH (I: r = 0.61, p<0.05; II: r = 0.67, p<0.05), and estradiol (II: r = 0.62, p<0.05) in early puberty. From pubertal stage II, inhibin B lost this relationship to gonadotropins and estradiol. Serum inhibin B and FSH levels increased significantly during pubertal development, with the highest peak found in stage III of puberty (133.5+/-14.3 ng/l), and decreased thereafter. In conclusion, inhibin B is produced in a specific pattern in response to gonadotropin stimulation and plays an important role in the regulation of the hypothalamic-pituitary-gonadal axis during childhood and puberty in girls. Inhibin B is involved in regulatory functions in developing follicles and seems to be a sensitive marker of ovarian follicle development.     

Age-related decline of plasma bioavailable testosterone in adult men

Plasma bioavailable and total testosterone (T), gonadotropins (FSH, LH) and prolactin (PRL) were determined in 70 ambulatory men subdivided into 3 groups according to age: group I (n = 22; age 20-35 yr), group II (n = 22; age: 36-50 yr) and group III (n = 26; age 51-70 yr). Bioavailable T levels declined significantly with age (r = -0.42; P less than 0.01) while those of total T decreased less significantly (r = -0.28; P less than 0.05). In addition, the decrease of bioavailable T occurred earlier. FSH was shown to increase with age (r = 0.41; P less than 0.01) whereas LH and PRL were not found to change significantly. Bioavailable T was correlated with total T (r = 0.25; P less than 0.05) and inversely correlated with FSH (r = -0.26; P less than 0.05). No correlation could be demonstrated between LH and either bioavailable or total T. In view of the age-related increase of sex hormone binding globulin, a fact generally observed in the literature, bioavailable T may be considered a more reliable index than total T for the evaluation of T production. Thus it may be concluded that the early decrease of bioavailable T in ambulatory men not known to have any pathology or any medication altering testicular function corresponds in fact to age-related decline of T secretion by the testes.     

Effect of Immobilization Stress on Gonadotropins and Sex Steroids

The effects of the acute immobilization stress on follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and testosterone levels in rats were evaluated. The male and female rats were grouped in control and stress groups (7 animals in each group). Vaginal smears were taken daily from female rats and the rats in the proestrus were involved in the experiments. After a 1-h immobilization stress, blood samples from the heart were taken and the serum FSH, LH, estradiol and testosterone levels were measured by radioimmunoassay (RIA). The results were statistically analyzed using the Mann–Whitney U-test. A statistically significant increase of the levels of FSH and estradiol, but not of LH, was found in the female rats after the stress. A statistically significant increase of the FSH concentration was also revealed in the male rats, but there were no significant changes of the LH and testosterone levels. The scientific and applied (medical) aspects of the data obtained are discussed.     

Effects of sympathetic denervation on follicular distribution,oestradiol and progesterone serum levels in prepubertal hemi-ovariectomized female guinea pig

The aim of this study was to determine the effects of maternal undernutrition during pregnancy on adult reproductive function in male and female offspring. Groups of ewes were fed rations providing either 100% (High, H) or 50% (Low, L) of estimated metabolisable energy (ME) requirements for pregnancy, from mating until day 95 of gestation, and thereafter were conventionally managed. At 20 months of age, LH and FSH profiles, and LH responses to exogenous GnRH were measured in male and female offspring and, in males, testicular responses to exogenous LH (as measured by testosterone concentrations) were also measured. Undernutrition had no effect on the mean birth weights of lambs of either sex, or on testicular size in male animals at either 6 weeks or 20 months of age. L males exhibited significantly higher FSH concentrations than H males (P < 0.05) but there were no differences with treatment in FSH profiles in females, basal LH profiles or gonadotrophin responses to GnRH in offspring of either sex, and no difference in basal testosterone concentrations or in the testosterone response to exogenous LH administration in males. Semen quality at 20 months of age was unaffected by pre-natal undernutrition but ovulation rate was significantly reduced in L compared to H female offspring (P < 0.05). It is concluded that pre-natal undernutrition had no effect on male reproductive development and adult function, but reduced ovulation rate in female progeny. This effect was not associated with a change in gonadotrophin profiles or pituitary responsiveness.     

Age-related changes in diurnal rhythms and levels of gonadotropins, testosterone, and inhibin B in male rhesus monkeys (Macaca mulatta)

Testosterone shows circadian rhythms in monkeys with low serum levels in the morning hours. The decline relies on a diminished frequency of LH pulses. Inhibin B shows no diurnal patterns. In elderly men, the diurnal rhythm of testosterone is blunted and inhibin levels fall. Here we explore whether aging exerts similar effects in the rhesus monkey. We collected blood samples from groups of young (6-9 yr) and old (12-16 yr) male rhesus monkeys at 20-min intervals for a period of 24 h under remote sampling via a venous catheter. We determined moment-to-moment changes in plasma levels of testosterone, FSH, and LH by RIA, and of inhibin B by ELISA. We found significant diurnal patterns of testosterone in both groups. The circadian rhythm in testosterone was enhanced in older monkeys. Testosterone levels and pulse frequencies dropped significantly below those of young monkeys during midday hours. Diminished pulse frequency of LH appeared to be responsible for the midday testosterone decrease in old monkeys, while LH and testosterone pulse frequency did not change in young monkeys at corresponding time points. Old monkeys showed extended periods of LH-pulse quiescence in the morning and midday hours. Inhibin B and FSH levels were generally lower in old monkeys compared with the young group, but neither inhibin B nor FSH showed circadian rhythms. We conclude from these data that old rhesus monkeys have a more prominent circadian rhythm of LH and testosterone resulting from an extended midday period of quiescence in the hypothalamus-pituitary-gonadal axis.     

Effects of corticosterone on the negative feedback action of testosterone, 5 alpha-dihydrotestosterone and estradiol in the adult male rat

Corticosterone acetate (10 mg/day) was administered to gonadectomized and adrenalectomized male rats bearing 5, 10 or 15 mm long testosterone filled silicone elastomer capsules. It was found that the serum testosterone levels induced by these capsules were not influenced by corticosterone treatment and that the weights of the prostates in the corticosterone treated rats were not different from their controls. In contrast, corticosterone acetate increased markedly the LH and FSH inhibitory effects of testosterone. Since several brain structures are able to convert testosterone into 17-beta-hydroxy-5-alpha-androstan-3-one (5-alpha-dihydrotestosterone) and/or estradiol, and these metabolites are probably involved in mechanisms controlling gonadotropin secretion, we studied also the effects of corticosterone on the feedback action of dihydrotestosterone and estradiol. 5 alpha-Dihydrotestosterone was administered by 5, 10 or 20 mm long elastomere capsules whereas estradiol was given by daily s.c. injections of 0.125, 0.25 or 0.50 micrograms estradiol benzoate. In the presence of corticosterone acetate the gonadotropin inhibitory action of testosterone, 5 alpha-dihydrotestosterone and estradiol increased more than 2 times.     

Phenotypic variation in testosterone and luteinizing hormone production among boars: differential response to gonadotropin releasing hormone and adrenocorticotropic hormone

Variation in ability of boars to produce testosterone and luteinizing hormone (LH) in response to both gonadotropin releasing hormone (GnRH) and adrenocorticotropic hormone (ACTH) stimulation, as well as quantitative relationships between pretreatment and posttreatment responses, were assessed in a population of 38 boars of similar age and breeding. Peripheral testosterone concentrations following either GnRH or ACTH increased (P less than 0.01) to peak circulating levels of 7.16 +/- 0.62 and 8.42 +/- 0.81 ng/ml by 120 and 45 min, respectively. Post-GnRH testosterone area varied from 7.44 to 50.84 ng/ml X h (CV = 47.44%) and post-ACTH testosterone area ranged from 3.05 to 28.78 ng/ml X h (CV = 46.09%). GnRH-induced increases in testosterone were preceded by elevations (P less than 0.01) in peripheral LH concentrations but ACTH had no effect upon LH levels. Post-GnRH area varied from 7.07 to 125.45 ng/ml X h (CV = 76.61%). Significant (P less than 0.01) correlations were obtained between pre-GnRH and post-GnRH testosterone areas (r = 0.58) and between pre-ACTH and post-ACTH testosterone areas (r = 0.67). Nonsignificant (P greater than 0.10) correlations were obtained between post-GnRH and post-ACTH testosterone areas (r = 0.006) and between post-GnRH testosterone and LH areas (r = 0.09). The testosterone producing ability of boars was highly variable and their innate ability to produce testosterone influenced their response to GnRH and ACTH. Additionally, the mechanisms by which GnRH and ACTH influence testosterone production in boars appear to differ. Variation in the ability of boars to produce testosterone could not be explained on the basis of differences in circulating levels of LH.