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The inhibitory effect of intracerebroventricularly injected interleukin 1beta on testosterone secretion in the rat: role of steroidogenic acute regulatory protein.

Exposure to disease or injury often results in impaired reproductive activity accompanied by decreased testosterone levels. After immune activation, the cytokine interleukin 1-beta (IL-1beta) circulates in high concentrations, and its exogenous administration evokes many of the sequelae of immune activation. Previously, we have shown that the administration of this cytokine into the cerebral ventricles blunts hCG-stimulated testosterone secretion. This effect, though time-dependent, occurs before significant elevation of interleukin 6 in the peripheral bloodstream, does not depend on adrenal activation, and/or changes in LH concentrations, leading us to hypothesize a direct connection between the brain and testis. To explore this mechanism further, we isolated testicular tissue from rats treated intracerebroventricularly (icv) with vehicle or IL-1beta 30 or 90 min before they were killed. We found that in vivo cytokine treatment blunted ex vivo testosterone secretion in response to hCG, showing that the mechanism is independent of circulating cytokines. Though hCG binding was moderately reduced by icv IL-1beta in these preparations, the extent of this inhibition did not explain our observations. As the first acutely and hormonally regulated step in the biosynthesis of testosterone is the transfer of cholesterol into the inner mitochondrial membrane, which is mediated by steroidogenic acute regulatory (StAR) protein, we hypothesized that the rapid effects of icv IL-1beta on testicular responsiveness to hCG might be due to reduced levels of StAR. We report here that StAR protein was indeed reduced in Leydig cells isolated from rats treated in vivo with IL-1beta. Furthermore, treatment with a water-permeable form of cholesterol that bypasses the requirement for StAR partially restored hCG-stimulated testosterone secretion from testes isolated from rats treated icv with IL-1beta. Taken together, our data indicate that StAR plays a role in the suppression of testicular function evoked by central administration of IL-1beta.

Animals↗

Differential effects of superior and inferior spermatic nerves on testosterone secretion and spermatic blood flow in cats.

It has been postulated that testosterone secretion is partially regulated by signals from the spermatic nerves. To further examine this hypothesis in vivo, the superior (SSN) or the inferior (ISN) spermatic nerves were stimulated electrically (varying intensity, 25 Hz, 0.2 msec, 10 min) in anesthetized cats, determining the testosterone concentration and the blood flow in the spermatic vein. In some additional experiments arterial blood was sampled, and norepinephrine (NE) output was calculated. Stimulation of the SSN (25-35 V) increased the testosterone concentration in spermatic vein blood (P < 0.01 compared with prestimulation levels). The response varied among animals, reaching a 50-100% increase in some animals, whereas in others it ranged from almost undetectable to more than 10 ng/100 g x min. Under the same experimental conditions, the NE output increased from 135.4 +/- 99 to 1614.2 +/- 347 pg/ml (P < 0.01), and spermatic blood flow decreased from 24.1 +/- 1.42 to 20.2 +/- 1.65 ml/min x 100 g (P < 0.05) during nerve stimulation. By contrast, stimulation of the ISN (25-35 V) modified neither the testosterone concentration, the NE output, nor the blood flow in the spermatic vein. High intensity stimulation (36-70 V) of each spermatic nerve evoked different vascular and hormonal effects. SSN activation induced a marked decrease in spermatic blood flow during stimulation and an increase in the testosterone response, whereas ISN activation resulted only in an enhanced spermatic blood flow. Our results suggest that testosterone secretion, although mainly dependent on gonadotropin secretion, could be further regulated by neural inputs from the SSN acting directly or alternatively through changes in blood flow. It would appear that the SSN mainly supplies the vasoconstrictor fibers to the testis, whereas the ISN provides vasodilator fibers.

Animals↗

Influence of nocturnal oxygen desaturation on circadian rhythm of testosterone secretion.

To investigate the influence of nocturnal oxygen desaturation on the circadian rhythm of testosterone secretion, polysomnography was performed on 2 consecutive nights in 24 male subjects who complained of loud snoring and/or obesity. During the first night, we collected blood samples every 4 h via a catheter and measured serum testosterone. We arbitrarily defined severe oxygen desaturation as that exceeding the baseline SaO2 by 4% during 80 min of total sleep time. The subjects were divided into 2 groups from the data of the second night; one was the severe desaturation group as mentioned above, and those who suffered less desaturation were classified as the free to mild oxygen desaturation group. We found that in the latter group peak testosterone levels appeared at 6 a.m. On the other hand, the severe desaturation group exhibited delayed peak testosterone levels, i.e. at 10 a.m. We calculated the ratio of the testosterone level at 10 a.m. to that at 6 a.m., and found a significant correlation between this ratio and total desaturation time (r = 0.446, p less than 0.05). These data suggest that severe oxygen desaturation may alter the circadian rhythm of testosterone secretion.

Adult↗

Effect of calcitonin and 1,25(OH)2-vitamin D3 on the FSH, LH and testosterone secretion at rest and LHRH stimulated secretion.

The calcium signal plays an important role in the control of the secretory process of some adenohypophyseal hormones which responds to the administration of calciotropic substances by a marked change. In the submitted work the effect of calcitonin and 1,25(OH)2-vitamin D3 (1,25(OH)2D3) on FSH, LH and testosterone secretion was investigated. A single dose of 50 U synthetic salmon calcitonin did not influence the FSH, LH and testosterone secretion at rest nor stimulated secretion. 1,25(OH)2D3 administered for four days in amounts of 3 micrograms/day did not affect the LH and testosterone secretion but increased slightly the secretory response of FSH to LHRH, significantly during the 80th minute following administration of the secretagogue (P less than 0.01). The indication of bi-phasic FSH secretion was eliminated by 1,25(OH)2D3. The significant decline of PTH levels following administration of 1,25(OH)2D3 is evidence of a biologically effective level of 1,25(OH)2D3 attained by the administered dose of hormone. As compared with the marked effect of calcitonin and 1,25(OH)2D3 on thyrotropic hormone secretion, it may be concluded that the gonadotropic system is considerably less sensitive to a change of calcium homeostasis induced by calcitonin or 1,25(OH)2D3. Nevertheless a slight increase of the FSH secretion and a change of the dynamics of its secretion suggest a modulating role of 1,25(OH)2D3 in the control of FSH secretion.

Adult↗

Moderate increases in peripheral blood estradiol concentration in the adult ram do not directly inhibit testosterone secretion.

Two experiments were conducted in July with adult Dorset x Leicester x Suffolk rams to determine whether increases of 150 or 300% in estradiol (E2) concentration in peripheral blood (from 6.3 +/- 0.8 pg/mL in control rams) would affect testosterone secretion directly as well as indirectly via the hypothalamic-pituitary axis. After 4 days of estradiol treatment (experiment 1) provided with subcutaneous polydimethylsiloxane implants filled with crystalline estradiol, luteinizing hormone (LH) and testosterone secretions were reduced by 50% (p < 0.05) in both groups of rams because of subtle decreases in pulse frequencies and amplitudes. Estradiol treatments were also associated with decreases in mean follicle-stimulating hormone (FSH) concentration (30-50% in both groups, p < 0.05) and increases in mean prolactin concentration (35% in low-E2 group; 105% in high-E2 group, p < 0.05), but testicular responsiveness to an LH challenge (single intravenous dose, 10 micrograms NIH-LH-S25) remained normal. When along with estradiol treatment, 10-micrograms doses LH were given every 80 min (experiment 2), testosterone secretion increased by 265% (p < 0.05) in both treated and control rams. Relative to day -1, secretion on day 4 was characterized by higher (p < 0.05) pulse frequencies and baseline concentrations and lower (p < 0.05) pulse amplitudes; values for all characteristics were similar to those for Dorset x Leicester x Suffolk rams in the breeding season. Interestingly, the decreases in mean FSH concentration brought about by estradiol and (or) LH treatments were not any greater than in experiment 1, and estradiol's ability to elevate mean prolactin concentration was blocked completely.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Early effects of pinealectomy on LH and testosterone secretion in white-tailed deer.

The early effects of pinealectomy on LH and testosterone secretion were studied in 11 white-tailed bucks. Six bucks were pinealectomized and three were sham-operated in early march at 9 months of age. Two unoperated bucks of the same age were also followed. The response of the pituitary gland and testis to LH releasing hormone (LHRH) was monitored for 2h each month for 1 year by radioimmunoassay of serum LH and testosterone. Prestimulation levels of LH (expressed as microgram NIH-oLH-S7) exhibited a cosinor curve pattern over the year (P less than 0.002) with levels ranging between 0.1 and 3.9 micrograms/l. Highest levels in pinealectomized males occurred in May 2 months after surgery and in control (sham-operated and unoperated) males in August. Maximal LH response to LHRH was characterized by a double-peaked curve in serum LH with the early peak around 20 min and a later peak at about 2h after injection. Maximal response to LHRH occurred in May in pinealectomized bucks and in August in control bucks. Baseline testosterone concentrations and testosterone response to LHRH varied in a seasonal fashion throughout the 12-month period in control bucks (P less than 0.001) but not in pinealectomized bucks. Baseline testosterone concentration and testosterone response to LHRH rose within 2 months after surgery in pinealectomized bucks and remained relatively constant for the next 10 months. These data demonstrate an early effect of pinealectomy on LH and testosterone secretion in 9-month-old animals kept under conditions of natural photoperiod and suggest differences in the response to pinealectomy by the pituitary gland and testes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increases in testosterone secretion in adult rams with immunoneutralization of endogenous estradiol occur in the absence of increases in pulsatile LH release or testicular LH receptors.

The testes of the ram become more responsive to LH stimulation following immunoneutralization of endogenous estradiol. The possibility that testosterone secretion is facilitated by increased LH-binding activity in the testes was investigated in the present study conducted with adult Dorset X Leicester X Suffolk rams during the time of testicular recrudescence. Patterns of episodic LH release and testosterone secretion (days--5, 10 and 24) and LH-binding activity in testicular biopsy samples (days--1, 14 and 28) were assessed on the days indicated relative to the onset of passive immunization and the establishment of relatively low titres (approximately 1:200) of estradiol antiserum. During the experimental period, mean serum testosterone concentration increased by approximately 150% for the immunized rams as basal concentration and pulse amplitude increased, while all characteristics of testosterone secretion remained unchanged for the nonimmunized rams. Characteristics of LH release and the concentration of LH-binding sites in the testes, however, were always similar for both groups of rams. Further, group differences in FSH and PRL secretion and in the concentration of testicular FSH-binding sites did not occur. These results provide evidence for an estradiol direct (gonadotropin independent) negative-feedback component in the regulation of Leydig cell function in the ram.

Animals↗

Growth hormone secretion patterns in relation to LH and testosterone secretion throughout normal male puberty.

Pulsatile growth hormone secretion patterns were studied in relation to LH and testosterone release in 30 healthy prepubertal boys and 2 adult men. Plasma GH was measured every 10 min, plasma LH and testosterone every hour. Night-time GH secretion parameters were 2-3 times higher than daytime values. During daytime, mean GH level and the fraction of GH in pulses increased from Tanner stage G2 to G4 (p = 0.01); during night-time these parameters increased as well (p less than or equal to 0.1) and decreased from stage G5 to adulthood (p = 0.05). GH pulse number did not increase; the number of high-amplitude (greater than 8 micrograms/l pulses, however, increased from stage G2 to G4 (p = 0.05) during the day. Height velocity correlated with their number of high pulses during day and night (tau = 0.39, p less than 0.003). From stage G2 to G4 significant correlations were observed between nocturnal testosterone levels and GH secretion parameters (tau = 0.53-0.57), in contrast to nocturnal LH levels. It is concluded that during puberty 1. GH secretion increases as a result of an increased pulse amplitude; 2. there is no consistent correlation between GH and LH levels; 3. increasing nocturnal testosterone levels are correlated with the increasing GH secretion; therefore GnRH does not seem to influence GH secretion directly, but an indirect effect via testosterone is more conceivable, and 4. height velocity is correlated with the number of high GH pulses.

Adolescent↗

Detection of testosterone secretion from individual rat Leydig cells.

The purpose of the present study was to analyze testosterone secretion from individual purified Leydig cells, using a reverse hemolytic plaque assay (RHPA) as an approach for identifying and characterizing subtypes of Leydig cells. Leydig cells from adult rats and protein A-coated ovine erythrocytes were mixed and incubated for appropriate lengths of time in the presence or absence of antitestosterone antibody, hormones or an analog of cyclic AMP. The slides from RHPA were histochemically stained for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Results show that testosterone secreting cells can be clearly identified by the formation of hemolytic plaques. The proportion of plaque-forming cells increases with incubation time, reaching a plateau at 60 min in the presence of gonadotropin. It was observed that not all 3 beta-HSD positive cells form plaques. It is concluded that the purified Leydig cell population has cells with differential steroidogenic and androgen-secretory activities.

3-Hydroxysteroid Dehydrogenases↗

Inhibition of aromatization stimulates luteinizing hormone and testosterone secretion in adult male rhesus monkeys.

Experiments were conducted to examine the role of aromatization in the control of LH and testosterone secretion in adult male rhesus monkeys. Treatment of male monkeys (n = 7) with sc Silastic packets containing the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) resulted in 1.5- to 3-fold elevations in serum LH and testosterone concentrations in six of seven animals. Concurrent treatment of ATD-treated monkeys with small quantities of estradiol-17 beta (n = 4) abolished the stimulatory effect of ATD. During ATD treatment, peripheral estradiol levels were reduced by 30% and hypothalamic aromatase activity, as determined in vitro, was reduced 80-90%. The lack of androgenic or antiandrogenic activity of ATD was demonstrated by its inactivity in either a mouse seminal vesicle bioassay or a highly sensitive penile spine bioassay. Furthermore, ATD did not react with rat prostatic or hypothalamic cytosol androgen receptors. 1,4,6-Androstatriene-17-ol-3-one, a possible metabolite of ATD in vivo, did react with prostatic and hypothalamic androgen receptors, but possessed no antiandrogenic activity in either bioassay. Thus, treatment of adult males with an aromatase inhibitor that inhibits both peripheral and central aromatization, and which has no apparent antiandrogenic activity, results in stimulation of LH and testosterone secretion. These data demonstrate that aromatization of androgens to estrogens plays an important role in negative feedback regulation of LH secretion and maintenance of normal testosterone levels in adult male primates.

Androstatrienes↗

Effects of follicular fluid administration on serum bioactive and immunoreactive FSH concentrations and compensatory testosterone secretion in hemicastrated adult rats.

In adult rats, removal of one testis (hemicastration) results in an elevation of serum follicle-stimulating hormone (FSH) concentrations and a compensation in testosterone secretion by the remaining testis without a corresponding increase in testis size. To determine whether changes in FSH secretion and compensatory androgen production are related, serum testosterone concentrations were measured after inhibin-rich porcine follicular fluid was administered twice daily for 4 days to block the hemicastration-induced rise in FSH. Both serum immunoreactive FSH (immuno-FSH) and bioactive FSH (bio-FSH) concentrations were increased 4 days after hemicastration. The significant increase in serum immuno-FSH in hemicastrated animals was prevented by follicular fluid administration, whereas the serum bio-FSH activity and biologic to immunologic (B/I) ratios were increased in follicular fluid-treated animals. The follicular fluid-induced reduction in serum immuno-FSH had no effect on serum testosterone secretion in hemicastrated rats. Serum inhibin concentrations were reduced 27% in hemicastrated rats compared with intact controls, while administration of exogenous follicular fluid increased serum inhibin concentrations. An elevation in serum immuno-FSH secretion after hemicastration apparently is not required for the compensatory testosterone response. However, the observation of increased bio-FSH in hemicastrated and follicular fluid-treated animals raises questions about the importance of FSH quality (bioactivity), rather than quantity, for controlling testicular steroidogenic activity.

Animals↗

Propranolol stimulates testicular interstitial fluid formation and testosterone secretion in rats.

We investigated the effect of intratesticularly injected propranolol on testicular interstitial fluid (TIF) formation and on testosterone levels in the TIF of intact adult male Wistar rats (4-9 rats per group). dl-propranolol at doses of 0.6, 1.2, or 6.0 mg/kg was injected into the left (L) testis whereas the right (R) testis (control testis) received vehicle. dl-propranolol (6.0 mg/kg) caused a significant increase in both TIF volume (329%) and TIF levels of testosterone (257%) in the L testis but not in the R (control) testis 3 h post-injection. In rats treated simultaneously with human chorionic gonadotropin (hCG, 5 IU/rat, sc) the same dose or propranolol (6.0 mg/kg) significantly increased the stimulatory effect of hCG on testosterone secretion by 1.8-fold, but hCG did not modify the stimulatory effect of propranolol on TIF volume. These results demonstrate a direct stimulatory effect of propranolol on TIF volume and testosterone secretion, both under basal and hCG-stimulated conditions.

Animals↗

Attempts for identification of a chorionic gonadotrophin-like bioactivity in the rat placenta which stimulates the testosterone secretion of the fetal testis in vitro.

The bioactivity of rat placental extracts was evaluated using a fetal rat testis testosterone (FRTT) bioassay. It is based on the measurement of the increase in testosterone secreted in vitro by testes from 18.5-day-old fetuses in response to the addition of placental extracts. Placentas obtained on days 11.5, 12.5, 13.5, 14.5, 15.5, 17.5 and 19.5 and homogenized with a Potter homogenizer (1 placenta per ml incubation medium), increased the secretion of testosterone by 460, 690, 500, 300, 220, 200 and 170%, respectively. These extracts showed a high proteolytic activity capable of suppressing the bioactivity of 0.8 ng/ml LH added prior to the extraction procedure. However, the bioactivity of the placental extracts did not increase after inhibiting placental proteases by the addition of benzamidine. Heat treatment did not decrease the bioactivity of placental extracts obtained without inhibition of proteases. Ultrafiltration of the placental extracts obtained with inhibition of the proteases showed that most of the bioactivity was dialyzable. The levels of bioactive material with molecular weights greater than 10,000 were very low (0.06 ng LH equivalent/placenta on day 12.5 and less than 0.02 ng LH equivalent/placenta on day 14.5). These results suggest that rat placental bioactivity as measured with the FRTT bioassay is due, for the most part, to steroid precursors of testosterone and, for a very small part, to an LH/chorionic gonadotrophin (CG)-like molecule. Furthermore, after day 14.5, the placental LH/CG-like bioactivity, if it exists, is synthesized in too low levels to be able to control the testicular activity in the rat fetus.

Animals↗

Influence of season and low-level oestradiol immunoneutralization on episodic LH and testosterone secretion and testicular steroidogenic enzymes and steroidogenic acute regulatory protein in the adult ram.

The regulation of LH-dependent and -independent increases in testosterone secretion by key proteins in the testes of adult rams was investigated. Serial blood samples were collected from groups of four control and passively immunized (oestradiol antiserum for 3 weeks) rams and the animals were gonadectomized in either the non-breeding season (April) or the breeding season (September). LH pulse frequency and basal (interpulse) concentrations were several times greater (P < 0.01) in the breeding season than in the non-breeding season. Neither of these parameters nor LH pulse amplitude were affected by oestradiol immunization. Parameters of testosterone episodic secretion and response to an injection (i.v.) of 15 micrograms NIH-LH-S25 were also greater (P < 0.05) in the breeding season and, with the exception of pulse frequency, in immunized rams versus controls. Substrate utilization established that testosterone biosynthesis was predominantly via the 5-ene pathway. Increases in blood testosterone concentration in the breeding season were associated with a fivefold higher (P < 0.01) activity of cytochrome P450 17alpha-hydroxylase/C-17,20 lyase (P450(17alpha)) and a 65% higher (P < 0.05) relative amount of mRNA for cytochrome P450 cholesterol side-chain cleavage enzyme complex (P450scc) in the testis. Of the steroidogenic enzyme activities examined, only that for 17beta-hydroxysteroid dehydrogenase (17beta-HSD) tended to be increased by oestradiol immunization. Blood concentrations of cholesterol lipoproteins and expression of the testicular low density lipoprotein receptor were not affected by season or immunization. The amount of steroidogenic acute regulatory protein (StAR) mRNA was 65% higher (P < 0.01) in the breeding season and 20% higher (P < 0.01) in immunized rams versus controls. These results indicate that greater LH stimulation may increase testosterone biosynthesis in the breeding season by increasing StAR mRNA (and presumably delivery of cholesterol to P450scc) and the activity of P450(17alpha), and possibly that of P450scc (activity not measured). More moderate increases in StAR mRNA and 17beta-HSD activity may explain, in part, the increases in testosterone secretion with oestradiol immunization.

17-Hydroxysteroid Dehydrogenases↗

Developmental change in the ability of estradiol to suppress testosterone secretion by the testis of the rat.

An intratesticular site of action has been proposed for the ability of estradiol (E2) to suppress testosterone secretion. Because testicular testosterone and E2 secretion as well as E2 receptors change during development, a physiologic role for E2 is possible. The present experiments compared the testes from 12-day-old and adult rats for the capacity of in vivo estradiol treatment to change in vitro androgen secretion in response to luteinizing hormone (LH) and dibutyryl cyclic AMP (Bt2cAMP). After 5 days in vivo treatment, in vitro responsiveness was estimated by radioimmunoassay (RIA) measurement of androgen secretion elicited by various doses of NIAMDD-LH-24 or 1.0 mM Bt2cAMP. Five days of E2 alone (500 ng/g BW s.c. once daily) markedly inhibited basal, LH-stimulated and Bt2cAMP-stimulated androgen production at both ages. Similar treatment of infant rats with LH (100 ng NIAMDD-LH-24/g BW) caused an increase in basal and LH-stimulated androgen secretion in vitro, but had no effect on the response to Bt2cAMP. The same pretreatment of adults with LH had no effect on basal, but inhibited LH- or Bt2cAMP-stimulated androgen secretion. Combined treatment of infants with E2 and LH for 5 days had no effect on basal or maximally stimulated androgen production; the in vitro response to submaximal stimulation with LH was significantly inhibited. Combined E2/LH treatment of adults significantly decreased the basal production of androgens and the response to LH or Bt2cAMP. These results suggest a major difference between the response to E2 of the Leydig cells from the rats of the two ages tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of chronic chloroquine treatment on prostaglandin and human chorionic gonadotropin (hCG) stimulation of testosterone secretion by the rat testis.

The effect of chronic chloroquine administration on prostaglandin E1 (PGE1) and human chorionic gonadotropin (hCG) stimulation of testosterone secretion by the rat Leydig cells was studied. Adult albino (Wistar strain) rats were injected with 4 mg/kg body weight of chloroquine phosphate every other day for 30 days. At the end of the period of treatment, the rats were sacrificed and the Leydig cells incubated with hCG and/or PGE1 for 3 hrs. The amount of testosterone secreted was estimated by radioimmunoassay. Chronic chloroquine treatment did not affect the activity of the Leydig cells and combined PGE1 and hCG did not show any additive effects.

Alprostadil↗

Tumor necrosis factor and interleukin-1 stimulate testosterone secretion in adult male rat Leydig cells in vitro.

The actions of two cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), on testosterone production by dispersed adult testis cells and purified Leydig cells in culture were studied. In one set of experiments, testis cells from adult (90-day-old) rats were enzymatically dispersed. In another set of experiments, the dispersed testis cells were placed on a Percoll density gradient and were centrifuged to yield purified (greater than 85%) Leydig cells. Both whole testis cells and purified Leydig cells were cultured in the presence of varying doses of TNF or IL-1 with or without maximally stimulating doses of human chorionic gonadotropin (hCG). Both TNF and IL-1 stimulated basal secretion of testosterone in whole testis cells, as well as purified Leydig cells. Additionally, both TNF and IL-1 augmented maximally hCG stimulated testosterone secretion. Both cytokines stimulated testosterone secretion by dispersed testis cells as early as 4 hours, and the effect continued for up to 72 hours. The cytokines slightly, but significantly, stimulated testosterone production in purified Leydig cells after 24 hours, and continued for up to 72 hours. We have concluded from this data that TNF and IL-1 stimulate the testosterone secretion by adult rat Leydig cells. While this effect might be mediated through the action of the cytokines on testicular macrophages, there might also be a direct effect on the Leydig cell since augmentation of secretion occurred in purified Leydig cells, as well as whole testis cells. Therefore, TNF and IL-1 may serve as local regulators of Leydig cell function.

Animals↗

Evidence that estrogen regulation of testosterone secretion in adult rams is mediated by both indirect (gonadotropin dependent) and direct (gonadotropin independent) means.

Involvement of endogenous estrogen in the regulation of gonadotropin and testosterone secretion was investigated in adult rams. Groups of four rams were either passively immunized against estradiol or treated with the antiestrogen tamoxifen for 2 weeks during the breeding season (October). Circulating testosterone levels in immunized rams increased eight-fold to supraphysiologic values as episodic elevations and baseline levels increased in magnitude; only moderate increases in LH peak frequency and magnitude occurred, and prolactin fell to undetectable levels. Tamoxifen treatment was not associated with changes in mean hormone levels, although there was a tendency toward reductions in the magnitude of episodic LH and testosterone secretion. When rams were challenged with exogenous GnRH and LH, a greater testicular endocrine response was observed in the immunized rams and the pituitary endocrine response was delayed in the tamoxifen-treated rams. Results indicate that in the ram 1) circulating levels of estradiol provide negative feedback signals of different intensities to the testis and the hypothalamic-pituitary axis and 2) tamoxifen exerts a mild estrogenic effect when administered at the dose of 25 mg/day.

Animals↗