Interactions of human growth hormone and prolactin on pituitary and Leydig cell function in adult transgenic mice expressing the human growth hormone gene

Adult male transgenic mice expressing the human growth hormone (hGH) gene are hypoprolactinemic. To evaluate the effects of exogenous prolactin (PRL) and endogenously secreted hGH on pituitary and Leydig cell function, adult male transgenic and nontransgenic mice (10-16 wk of age) were treated s.c. with either saline-polyvinylpyrrolidone (PVP) or oPRL (100 micrograms/mouse) in saline-PVP. Animals were treated twice daily; a total of 7 injections were given. One hour after the last injection, each group of mice was treated i.p. either with saline or oLH (0.3 microgram/g BW); 2 h later, blood was obtained via heart puncture. Plasma FSH, LH, PRL, androstenedione (A-dione), and testosterone (T) levels were measured by validated RIAs. Basal PRL levels were significantly lower (p less than 0.001) and basal LH concentrations were significantly higher (p less than 0.01) in transgenic than in nontransgenic mice. Administration of PRL significantly decreased (p less than 0.01) plasma LH levels in transgenic mice, whereas similar treatment of nontransgenic mice increased (p less than 0.01) circulating LH concentrations. Plasma FSH levels were unaffected in transgenic and nontransgenic mice treated with saline or PRL. Basal plasma A-dione and T levels were similar in both groups of animals and were significantly increased after treatment with LH. Administration of PRL increased T levels in transgenic and nontransgenic mice, but the T response to LH treatment was greater in PRL-treated transgenic mice, indicating the synergistic effect of hGH in the biosynthesis of T.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of acutely increased plasma testosterone concentrations on pulsatile luteinizing hormone secretion in the male rat

To assess the role of testosterone (T) in regulating the minute-to-minute release of pulsatile luteinizing hormone (LH) secretion in the adult male rat, we investigated the negative feedback of acute increases in plasma T concentrations on pulsatile LH secretion in acutely castrated male rats. At the time of castration, we implanted T-filled Silastic capsules, s.c., which maintained plasma T concentrations at approximately 1.8 ng/ml and suppressed LH pulses. On the next day, the capsules were removed; blood sampling (every 6 min) was started 8 h after implant removal, thereby allowing LH pulses to be reinitiated. Immediately following a control bleeding interval of 2 h, either T or vehicle alone was infused s.c., and blood sampling continued for another 4 h. In animals receiving vehicle alone, LH pulse frequency and mean LH levels increased over the 6 h bleeding period. The administration of 200 ng T/min caused a rapid rise in plasma T concentrations of about 4 ng/ml ("physiological") and prevented the increase in pulse frequency that occurred in the control group; it did not, however, reduce pulse frequency over the 4 h infusion period. When T was infused at the rate of 400 ng/ml, plasma T concentrations rose to approximately 18 ng/ml ("supraphysiological") and LH pulse frequency was significantly reduced, but not completely inhibited, during the last 2 h of the infusion. The pulse amplitude of luteinizing hormone did not change significantly in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lithium: Short-term and chronic effects on plasma testosterone and luteinizing hormone concentrations in mice

The effects of short-term and chronic lithium administration on the concentrations of plasma testosterone (T) and luteinizing hormone (LH) were evaluated in C57BL/6 mice, maintained on a fixed photo-period of LD 14:10 (white lights on at 06:00 h, CST). Lithium chloride was injected intraperitoneally twice daily (at 09:00 and 16:00 h) in groups of adult male mice at a dosage of 2.5 meq/kg for 7 days, and 1.25 meq/kg for 21 days. Circulating levels of T and LH were measured by standard radioimmunoassay (RIA) methods. Plasma T levels showed a significant increase in mice treated with lithium for 7 days as compared to those in saline-injected control animals. However, there was no significant difference in the concentrations of plasma T between chronic (21 days) lithium-treated mice and the matched control. Plasma LH levels remained unchanged following both short-term and chronic lithium treatment.     

Effects of chronic D-Leu6, des-Gly10-gonadotropin releasing hormone ethylamide on male sex tissues

The chronic administration of superactive agonists of gonadotropin releasing hormone (GnRH-A) have been reported to have a direct inhibitory effect on the sex tissues of the male rat. In an attempt to confirm or refute this statement, adult male rats were either left intact or were castrated and then treated daily for 14 days with either testosterone (T), dihydrotestosterone (DHT) or sesame oil (vehicle). Half of the intact and castrate animals also received daily injections of 200 ng of the GnRH agonist, D-Leu6, des-Gly10-GnRH ethylamide for 14 days. Twenty-four hours after completing treatment, blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and T were measured by radioimmunoassay and the ventral prostate gland (VP), seminal vesicle (SV) and penis were weighed. After 2 weeks of GnRH-A treatment, the plasma T level was reduced from 2506 +/- 170 (pg/ml +/- SEM) in the intact, nontreated animals to 907 +/- 69 in the intact, GnRH-A-treated group, indicating that the dosage of GnRH-A used in this study had an inhibiting effect on T secretion. No differences were observed in the VP, SV and penile weights between the castrate, GnRH-A and the castrate, nontreated groups. When exogenous T or DHT was given for 14 days to these castrated animals, the concomitant administration of GnRH-A did not appear to have any effect on the plasma T levels or the sex accessory tissue weights. These data suggest that GnRH-A itself does not appear to have a direct inhibitory or stimulatory effect on the sex tissues of the adult male rat.     

Effects of testosterone metabolites on serum gonadotropin concentrations in immature male rats.

The ability of testosterone, androsterone, 5alpha-androstane-3alpha,17beta-diol, and 5alpha-androstane-3beta,17beta-diol to prevent the castration-induced rise in serum gonadotropin levels was investigated in immature male rats. Rats castrated at 30 days of age were treated once per day by subcutaneous injection of 12.5-100 mug of the steroid per 100 g body weight per day for 3 days, beginning on the day of castration. The animals were sacrificed 24 h after the last injection. Testosterone propionate, androsterone propionate, and 5alpha-androstane-3alpha,17beta-diol dipropionate were also tested at the approximate molar equivalent of 100 mug of the free alcohol form per 100 g body weight per day. Testosterone propionate and 5alpha-androstane-3alpha,17beta-diol were the only compounds tested that prevented the castration induced rise in luteinizing hormone (LH) concentrations. Testosterone propionate also inhibited the rise in follicle stimulating hormone (FSH) concentrations whereas 5alpha-androstane-3alpha,17beta-diol inhibited the rise in FSH in one but not in another experiment. These were the only compounds tested that affected serum FSH concentrations. The lower doses of testosterone tested significantly increased serum LH, but not FSH concentrations compared to castrate control animals. The highest dose tested partially inhibited the rise in serum LH concentrations. Both androsterone and androsterone propionate maintained ventral prostate weights. Although neither compound prevented the castration induced rise in serum LH, two groups receiving androsterone had serum LH concentrations significantly lower than the castrate control group. 5alpha-Androstane-3beta,17beta-diol and 5alpha-androstane-3alpha,17beta-diol dipropionate failed to maintain ventral prostate weights or prevent the rise in serum gonadotropin levels. These results indicate that 5alpha-androstane-3alpha,17beta-diol is capable of preventing the castration induced rise in serum LH concentrations in the immature male rat and thus may participate in the regulation of LH secretion in these animals.     

Inhibition of pituitary-gonadal function in male rats by a potent GnRH antagonist

The inhibitory effects of the potent GnRH antagonist, [Ac-D-pCl-Phe1,2,D-Trp3,D-Arg6,DAla10]GnRH (GnRHant) upon pituitary-gonadal function were investigated in normal and castrated male rats. The antagonist was given a single subcutaneous (s.c.) injections of 1-500 micrograms to 40-60 day old rats which were killed from 1 to 7 days later for assay of pituitary GnRH receptors, gonadal receptors for LH, FSH, and PRL, and plasma gonadotropins, PRL, and testosterone (T). In intact rats treated with low doses of the antagonist (1, 5 or 10 micrograms), available pituitary GnRH receptors were reduced to 40, 30 and 15% of the control values, respectively, with no change in serum gonadotropin, PRL, and T levels. Higher antagonist doses (50, 100 or 500 micrograms) caused more marked decreases in free GnRH receptors, to 8, 4 and 1% of the control values, which were accompanied by dose-related reductions in serum LH and T concentrations. After the highest dose of GnRHant (500 micrograms), serum LH and T levels were completely suppressed at 24 h, and serum levels of the GnRH antagonist were detectable for up to 3 days by radioimmunoassay. The 500 micrograms dose of GnRHant also reduced testicular LH and PRL receptors by 30 and 50% respectively, at 24 h; by 72 h, PRL receptors and LH receptors were still slightly below control values. In castrate rats, treatment with GnRHant reduced pituitary GnRH receptors by 90% and suppressed serum LH and FSH to hypophysectomized levels. Such responses in castrate animals were observed following injection of relatively low doses of GnRHant (100 micrograms), after which the antagonist was detectable in serum for up to 24 h. These data suggest that extensive or complete occupancy of the pituitary receptor population by a GnRH antagonist is necessary to reduce plasma gonadotropin and testosterone levels in intact rats. In castrate animals, partial occupancy of the available GnRH receptor sites appears to be sufficient to inhibit the elevated rate of gonadotropin secretion.     

Circadian variations in plasma LH and FSH in juvenile and adult male mice

Experiments were performed to ascertain circadian fluctuations in plasma levels of LH and FSH in juvenile and adult male mice. Animals under natural lighting (11 h day/13 h night) were killed at 1-hour intervals over a 24-hour period. There were large variations in plasma LH concentrations between animals sacrificed within each killing period. Baseline LH levels (values lower than 60 ng/ml) showed a significant 24-hour periodicity in adult males. FSH concentrations exhibited significant diurnal variations in juvenile and adult males. There was significant influence of age on the temporal pattern and 24-hour mean plasma hormone levels.     

Effects of lithium on the pituitary-gonadal axis in the rat: evidence for dose-dependent changes in plasma gonadotropin and testosterone levels

The purpose of the present study was to examine the effects of lithium, a drug which is now used rather widely in the treatment of acute mania and the prophylaxis of manic-depressive bipolar disorders, on the pituitary-gonadal function in the laboratory rat. Sexually adult male rats, maintained under standardized laboratory conditions (LD 14: 10; lights on at 06:00 h, CST), were injected (ip) with lithium chloride both acutely for 1 day and chronically for 5 days, and by utilizing a low and high dose. For the low dose, lithium was injected twice daily (at 10:00 and 15:00 h) at 2.5 meg/Kg for 1 and 5 days, whereas in the high dose groups, also receiving lithium twice daily and at the same hours, the dosages were 5 meq/Kg for 1 day and 3.5 meq/Kg for 5 days. Animals were sacrificed 4 hours after the last lithium (or saline) injections. Plasma and pituitary levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and plasma levels of testosterone (T) were measured by radioimmunoassay (RIA). The administration of the low dose led to a significantly higher (P less than 0.001) plasma FSH, but unaltered plasma LH, levels after 5 days. In contrast, the high dose lithium led to significant suppressions of plasma LH (P less than 0.02; on day 5) and FSH (P less than 0.001; on both day 1 and 5) levels. The levels of plasma T also showed a significant reduction following the low dose (P less than 0.02; on day 5), as well as the high dose lithium treatment, as evident after both 1 (P less than 0.02) and 5 (P less than 0.02) days. Regardless of the dosage, or the duration of treatment, pituitary gonadotropin levels remained unaltered following lithium. The results of our present experiments suggest that lithium administration, either acutely or on a chronic basis, might be associated with significant adverse effects on the pituitary-testicular axis. Furthermore, since some of the hormonal changes were evident when plasma lithium concentration was within the therapeutic range, our data may have potential clinical implications.     

Effects of a major androgen-dependent urinary protein, alpha 2u-globulin on the pituitary-gonadal axis and hypothalamic monoamines in adult male mice.

The purpose of the present study was to evaluate the effects of alpha-2u-globulin, a sex-dependent male rat urinary protein on pituitary-gonadal functions and hypothalamic monoamine contents in male mice. Adult male mice, maintained under standardized laboratory conditions (L:D, 14:10) were injected subcutaneously with alpha-2u-globulin at a dose of 1 mg/animal/day or with vehicle daily for 14 days and killed 16 h after the last injection. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and testicular levels of T were measured by radioimmunoassays. The concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in medial basal hypothalamus (MBH) and anterior hypothalamus (AH) were measured by high performance liquid chromatography. Administration of alpha-2u-globulin led to a significant increase in plasma FSH and LH levels (P less than 0.05) as well as in plasma and testicular T levels (P less than 0.025). In the MBH of alpha-2u-globulin treated mice, there were significant elevations of NE (P less than 0.025), DA (P less than 0.01) and 5-HT (P less than 0.025) contents. In the AH, both DA (P less than 0.025) and 5-HT (P less than 0.01) contents were decreased while NE content remained unaltered. These results indicate that administration of alpha-2u-globulin can lead to a significant stimulation of pituitary-testicular axis and that this effect may be mediated through alteration of hypothalamic monoamines.     

Seasonal changes in the reproductive organs and plasma and pituitary hormone content of the male Bennett's wallaby (Macropus rufogriseus vufogriseus)

In a number of species of seasonally breeding marsupial, the male is fertile throughout the year but there is a marked seasonal change in weight of the accessory sexual glands. In this study, body weight, prostate, epididymis and testis weights and plasma concentrations of testosterone, LH and prolactin and pituitary content of LH and prolactin were determined in male Bennett's wallabies shot at 1–2 month intervals over a period of 17 months. There was a highly significant increase in prostate weight which was coincident with the breeding season for this species. A small but significant increase in testis weight was also observed but epididymis weight remained unchanged. Plasma testosterone concentrations were significantly increased at a time coincident with the increase in prostate weight. Plasma prolactin and LH concentrations were low in most animals and remained unchanged during the study. In contrast, pituitary prolactin and LH contents showed highly significant changes, with increasing and peak hormone content preceding maximum prostate weight and plasma testosterone concentrations by several months. While these latter results suggest a role for prolactin and LH in the seasonal control of the reproductive organs in the male wallaby, a more intensive study of the pattern of secretion of these hormones and possibly more sensitive hormone assays are required to understand their relative roles in regulating the annual cycle of prostate growth.     

Influence of perinatal androgenization on the castration response of adult rats

An unexplained dichotomy exists between the LH (luteinizing hormone) responses to castration of male and female rats, as males show a more prompt increase in serum LH levels. We have tested the hypothesis that neonatal exposure to androgen determines the sexual dimorphism of that response. Control groups of male and female rats were castrated at 60 days of age. Other animals had been castrated at 0 or 25 days of age and then given steroid treatment via testosterone (T) implants from 25 through 60 days of age. At 60 days of age a blood sample was taken from each animal before removal of either the T implant or the gonads. Animals were bled again 24 and 48 h later. Within 24 h after orchidectomy the typical early plateau of plasma LH had occurred, represented by an increment in mean LH concentrations of 316 ng/ml. Orchidectomy at 25 days of age had little or no effect on subsequent response to removal of T. In contrast, neonatal orchidectomy resulted in a markedly diminished response to T removal on Day 60. The response, however, was not reduced to that of normal females. In female rats plasma LH does not increase by 48 h after ovariectomy. Perinatal testosterone propionate (TP) treatment of females partially masculinized (enhanced) the LH response to T implant removal, but only if ovariectomy had been performed prior to puberty (at 0 or 25 days of age).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of cocaine hydrochloride on the male reproductive system

The reproductive system effects of cocaine were studied in male rats. The analysis included measurements of circulating levels of luteinizing hormone (LH) and testosterone (T) by radioimmunoassay (RIA). The weights of the testes and sex accessory organs were also assessed and compared with control animals. Dosage level, duration of treatment, and interval between injection and sacrifice were the parameters examined. Following a single intraperitoneal (IP) injection, LH levels decreased over a 3-hour period. At a high dosage (40 mg/kg), cocaine caused a significant elevation in serum T followed by a significant depression of T for at least 2 hours. When administered chronically for 15 days, the low dose group (10 mg/kg) did not vary significantly from the vehicle controls. However, the high dose group had lower LH and T levels, as well as correspondingly lighter weight seminal vesicles and epididymis. No changes were noted in the weights of the ventral prostate or testes. This research suggests that cocaine acts primarily at the hypothalamic-hypophyseal axis with a possible secondary action at the gonadal level.     

Effects of a gonadotropin-releasing hormone agonist implant on reproduction in a male marsupial, Macropus eugenii

This study evaluated the potential of slow-release GnRH agonist (deslorelin) implants to inhibit reproductive function in the male tammar wallaby. The specific aim was to measure the effects of graded dosages of deslorelin on testes size and plasma LH and testosterone concentrations. Adult male tammar wallabies were assigned to four groups (n = 6 per group) and received the following treatment: control, placebo implant; low dose, 5 mg deslorelin; medium dose, 10 mg; high dose, 20 mg. All dosages of deslorelin induced acute increases (P < 0.001) in plasma LH and testosterone concentrations within 2 h, with concentrations remaining elevated during the first 24 h but returning to pretreatment levels by Day 7. Thereafter, there was no evidence of a treatment-induced decline in plasma testosterone concentrations. There was no detectable difference in basal LH concentrations between treated and control animals, nor was there a significant change in testes width or length (P > 0.05). These results suggest that the male tammar wallaby is resistant to the contraceptive effects of chronic GnRH agonist treatment. Despite the maintenance of testosterone secretion, the majority of male tammars (10 of 17) failed to respond to a GnRH challenge with a release of LH between Days 186 and 197 of treatment. The failure of animals to respond to exogenous GnRH suggests a direct effect of deslorelin on the pituitary, resulting in a level of desensitization that was sufficient to inhibit a LH surge but insufficient to inhibit basal LH secretion. The variation between animals is believed to result from earlier recovery of some individuals, in particular those that received a lower dose, or individual resistance to the desensitization process.     

Luteinizing hormone and testosterone secretory profiles of boars: Effects of stage of sexual maturation

Two short term studies of LH and testosterone secretory profiles were carried out to evaluate the effects of stage of sexual maturity on the patterns of secretion of these hormones in Large White x Landrace boars. Four pubertal and three post-pubertal boars were subjected to plasma sampling every twenty minutes for 24 hours. During puberty, plasma profiles of LH varied in a manner indicative of a highly pulsatile mode of secretion. Likewise, large fluctuations in plasma testosterone levels were noted at this age, but they were not as frequent as those of LH. In contrast, plasma LH and testosterone profiles of post-pubertal boars showed fewer and smaller fluctuations in hormone concentrations. The overall mean levels of LH and testosterone were 0.82 and 1.04 ng/ml in pubertal boars, and 0.39 and 0.81 ng/ml in post-pubertal animals. At neither age was there any evidence of diurnal variations in plasma hormone concentrations.     

Effects of cranial cervical ganglionectomy and castration of male lambs. III. Hormonal responses following administration to gonadotrophin releasing hormone (GnRH)

Entire and castrate male lambs, which were cranial cervical ganglionectomized (GX) or untreated, were utilized in a study of responses to intravenous GnRH; 24 animals were treated at both 101 and 277 days of age. GX caused a reduction in basal LH concentrations of both wethers and rams at the first sampling, but increased pre-injection levels of this hormone in 277 day old wethers. Basal LH levels of castrates were substantially higher than those of entires, but GX had no significant influence on pretreatment testosterone secretion in rams. GnRH treatment elevated plasma LH levels in all animals, while in entires increases in testosterone concentrations also occurred. Castration significantly increased peak LH levels together with total LH output. At neither age were the LH or testosterone reponses influenced significantly by GX, nor was the interaction of castration and GX significant for LH response data. The major effect of age at GnRH treatment was that markedly higher testosterone responses were recorded from the older rams.     

Effects of gonadotropin-releasing hormone administration on the pituitary-gonadal axis in male and female dogs before and after gonadectomy

GnRH-stimulation tests were performed in 14 female and 14 male client-owned dogs of several breeds, before and 4 to 5 mo after gonadectomy. The aim of the study was to obtain more insight into the pituitary-gonadal axis in intact and neutered dogs and to establish reference values. Basal plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were increased significantly after gonadectomy in both bitches and male dogs. In both males and females ranges of the basal plasma FSH concentrations, before and after gonadectomy, did not overlap as opposed to the overlap in ranges of the basal plasma LH concentrations. Before gonadectomy basal plasma LH concentrations were lower and basal plasma FSH concentrations were higher in bitches than in male dogs. After gonadectomy these basal values did not differ significantly. GnRH administration before gonadectomy resulted in an increase in plasma LH and FSH concentrations in both genders. GnRH administration after gonadectomy produced an increase only in plasma LH concentrations in both genders, and a just significant increase in plasma FSH in castrated male dogs. GnRH administration before gonadectomy resulted in a significant increase in plasma testosterone concentration in both genders. In males ranges of basal and GnRH-stimulated plasma testosterone concentrations before and after gonadectomy did not overlap. Basal plasma estradiol concentrations were significantly higher in intact males than in castrated males and their ranges did not overlap. The basal estradiol concentrations in bitches before and after ovariectomy were not significantly different. At 120 min after GnRH administration, ranges of plasma estradiol concentration of intact and ovariectomized bitches no longer overlapped. In conclusion, basal plasma FSH concentration appears to be more reliable than basal plasma LH concentration for verification of neuter status in both male and female dogs. The basal plasma testosterone concentration appears to be reliable for verification of neuter status in male dogs. The plasma estradiol concentration at 120 min after GnRH administration can be used to discriminate between bitches with and without functional ovarian tissue.     

Differential effects of follicle-stimulating and luteinizing hormones on testosterone production by mouse testes

In adult mice, direct intratesticular injection of ovine follicle-stimulating hormone (o-FSH-13; AFP 2846-C, from NIAMDD, less than 1% LH contamination) at 10, 100 or 1000 ng significantly elevated concentrations of testosterone (T) within the testis. These effects were rapid, with peak values attained by 15 min, and transient, with return to values comparable to that in the contralateral, saline-injected testis within 90 min. Intratesticular injection of FSH (1 microgram) significantly increased testicular T levels in 15- and 60-day old mice. This contrasted with the effects of intratesticular administration of human chorionic gonadotropin (hCG), which stimulated T production significantly at 30 days of age through adulthood. In adult mice, the equivalent LH to the possible contamination in the FSH preparation (1 ng) had no effect. Intratesticular injection of 10 ng LH produced comparable stimulation to that by 100 ng FSH (approximately 7-fold). Systemic pre-treatment with a charcoal-treated porcine follicular fluid (PFF) extract for 2 days reduced plasma FSH levels [86 +/- 17 (5) vs 700 +/- 8 (6); P less than 0.05], but had no effect on plasma LH. Twenty-four hours after the last treatment, the response to intratesticular injection of hCG (2.5 mIU), FSH (100 ng) or LH (10 ng) was also significantly attenuated in these mice. Intratesticular injection of PFF had no direct effect on testicular T levels. In vitro T production in the presence of hCG, LH or FSH were differentially affected by the concentrations of calcium (Ca2+) or magnesium (Mg2+) in the incubation media. The stimulatory effects of FSH were apparent at significantly lower levels of Ca2+ or Mg2+, than were those of LH or hCG. The results of these studies indicate that FSH is capable of stimulating testicular T production. Furthermore, the responsiveness to FSH is qualitatively different than that to LH/hCG in terms of the age pattern, as well as the dependence on Ca2+ or Mg2+. In addition, plasma FSH levels appear to influence testicular responsiveness to direct exogenous administration of gonadotropins. These studies indicate that FSH stimulation of T production can be differentiated from those of LH, and that these effects of FSH can be observed under physiological conditions.     

Alteration in the normal pattern of serum testosterone and 5α-androstane-3α,17β-diol in the immature male rat following chronic treatment with luteinizing hormone releasing hormone or luteinizing hormone

A major component of sexual maturation in the male rat is a progressive decline in serum concentrations of 5α-androstane-3α,17β-diol (3α-diol) and a concomitant increase in testicular testosterone biosynthesis and secretion. Chronic administration of synthetic luteinizing hormone releasing hormone (LHRH) or luteinizing hormone (LH)/human chorionic gonadotropin (hCG) to immature male rats has been shown to result in a delay in sexual maturation as evidenced by decreased sex accessory gland weights and altered testicular testosterone production. We have examined the postulate that such treatments may either reverse or retard the normal developmental pattern of serum testosterone and 3α-diol concentrations. Chronic $\text{in vivo}$ treatment of 28 day old immature male rats for 2 weeks with daily injections of either 0.5 μg of LHRH, 1.0 μg of LHRH, or 30 μg of LH was found to result in significant reductions in weights of the seminal vesicles and ventral prostate glands and diminutions in serum testosterone concentrations. Serum content of 3α-diol was either unchanged or slightly elevated in the LHRH treated animals and increased significantly in the LH treated animals. These data suggest that either a reversal of or retardation in the normal developmental pattern of serum testosterone and 3α-diol content has been achieved in the immature male rat by chronic LHRH or LH treatment.     

Effects of lithium chloride on testicular steroidogenic and gametogenic functions in mature male albino rats

The present study was undertaken to evaluate the effects of lithium, an antimanic drug, on steroidogenic and gametogenic functions of testis in the laboratory rat. Adult male rats of Wistar strain maintained under standard laboratory conditions (L:D, 14h:10h), were injected (S.C) with lithium chloride at the dose of 0.1 mg, 0.2 mg and 0.4 mg/100 g body weight/day for 21 days. All the treated animals along with the vehicle treated controls were sacrificed 24 hours after the last injections. Testicular steroidogenic activity was evaluated by measuring the activities of two steroidogenic key enzymes, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta hydroxysteroid dehydrogenase (17 beta-HSD). Gametogenic capacity was determined by counting the number of germ cells at stage VII of seminiferous cycle. Plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone (T) were measured by radioimmunoassay (RIA). Administration of lithium chloride at a dose of 0.1 mg/100 g body wt. for 21 days led to insignificant changes of plasma FSH, LH, PRL and T along with unaltered activities of testicular delta 5-3 beta-HSD, 17 beta-HSD activities and gametogenesis. In contrast, 0.2 mg of lithium treatment for 21 days causes a significant reduction of plasma FSH (P less than 0.01), LH (P less than 0.001), PRL (P less than 0.001) and T (P less than 0.001) along with inhibition of testicular delta 5-3 beta-HSD activity (P less than 0.01) and 17 beta-HSD activity (P less than 0.001). Gametogenic activity does not exhibits any significant reduction in the number of preleptotene spermatocytes (PLSc) and midpachytene spermatocytes (mPSC) while significant reduction in the number of spermatogonia A (Asg) (P less than 0.01) and Step 7 spermatids (7Sd) (P less than 0.001) were observed at stage VII of seminiferous cycle when compared to control. The degree of detrimental effects of lithium on testicular activity became more prominent at the dose of 0.4 mg/100 g body wt. The results of our experiments suggest that lithium administration might be associated with significant adverse effects on testicular activities. Furthermore, since hormonal changes and altered gametogenic activities were evident when plasma lithium concentration was below or within the therapeutic range, our data may have some potential clinical implications.     

Suppression of pulsatile luteinizing hormone secretion by gonadotrophin-releasing hormone antagonist does not affect episodic progesterone secretion or corpus luteum function in ewes.

Progesterone secretion has been observed to be episodic in the late luteal phase of the oestrous cycle of ewes and is apparently independent of luteinizing hormone (LH). This study investigated the effects of suppressing the pulsatile release of LH in the early or late luteal phase on the episodic secretion of progesterone. Six Scottish Blackface ewes were treated i.m. with 1 mg kg-1 body weight of a potent gonadotrophin-releasing hormone (GnRH) antagonist on either day 4 or day 11 of the luteal phase. Six ewes received saline at each time and acted as controls. Serial blood samples were collected at 10 or 15 min intervals between 0 and 8 h, 24 and 32 h, and 48 and 56 h after GnRH antagonist treatment and daily from oestrus (day 0) of the treatment cycle for 22 days. Oestrous behaviour was determined using a vasectomized ram present throughout the experiment. Progesterone secretion was episodic in both the early and late luteal phase with a frequency of between 1.6 and 3.2 pulses in 8 h. The GnRH antagonist abolished the pulsatile secretion and suppressed the basal concentrations of LH for at least 3 days after treatment. This suppression of LH, in either the early or late luteal phase, did not affect the episodic release of progesterone. Daily concentrations of progesterone in plasma showed a minimal reduction on days 11 to 14 after GnRH antagonist treatment on day 4, although this was significant (P < 0.05) only on days 11 and 13. There was no effect of treatment on day 11 on daily progesterone concentration, and the timing of luteolysis and the duration of corpus luteum function was unaffected by GnRH antagonist treatment on either day 4 or day 11. These results indicate that the episodic secretion of progesterone during the luteal phase of the oestrous cycle in ewes is independent of LH pulses and normal progesterone secretion by the corpus luteum can be maintained with minimal basal concentrations of LH.