Effects of PRL and FSH on LH binding and number of Leydig cells in hypophysectomized mice

The effects of PRL and FSH on testicular LH receptors were studied in hypophysectomized (hypox) mice. From the eleventh day after hypophysectomy, they were given 100 micrograms ovine (o) PRL and/or 2 micrograms oFSH in two injections per day for 10 days. Hypophysectomy reduced the weight of testis, epididymides and seminal vesicles, and the LH binding to the testis. Treatment with oPRL and/or oFSH in hypox mice resulted in an increase in the weight of testis and epididymides, and the LH binding per testis. There was no difference between the testicular LH binding in oFSH- and oPRL-treated mice. Histological examination showed that oPRL and/or oFSH treatment in hypox mice restored normal spermatogenesis. Administration of oFSH to hypox mice led to an increase in the number of typical Leydig cells, whereas oPRL was not effective. These results suggest that either PRL or FSH stimulates the LH binding to the testis, but that the action of PRL and FSH on the increase in testicular LH binding is different.     

Hormonal regulation of testicular prolactin receptors and testosterone synthesis in golden hamsters

A study was conducted with hypophysectomized hamsters to determine effects of administration of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)-alone or in combination-on testicular PRL receptors and in vitro testosterone production. Hormonal injections commenced the second day after hypophysectomy, and hamsters were killed on Day 5, approximately 13 h after the last hormonal injection. PRL receptor numbers were reduced by hypophysectomy, and PRL administration alone lessened the extent of this decrease. By themselves, neither LH nor FSH affected PRL receptors, but a combination of PRL + FSH + LH produced the greatest effect on these receptors. Receptor affinity was only modestly affected by any treatments. In vitro testosterone synthesis was measured after addition of 0, 2, 10, and 50 mIU of human chorionic gonadotropin (hCG) to incubations of testicular tissue. Neither PRL nor FSH by themselves in vivo affected basal or hCG-stimulated testosterone production. However, PRL + FSH increased (p less than 0.05) the magnitude of the in vitro testosterone response to hCG, as well as the sensitivity of that response (slope of the dose-response curve). LH alone increased both basal and hCG-stimulated testosterone production. PRL + LH provided no additional increase in the magnitude of the testosterone response, but increased (p less than 0.05) the sensitivity. PRL + FSH + LH in vivo provided for the greatest sensitivity of the testosterone response to hCG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of postnatal treatment with a gonadotropin-releasing hormone antagonist on sexual maturation of male rats

The role of postnatal pituitary-testicular activity in sexual maturation at puberty was studied in male rats. Rats were injected twice daily with a potent gonadotropin-releasing hormone antagonist (N-Ac-4-Cl-D-Phe1, 4-Cl-D-Phe2, D-Trp3, D-Phe6, D-Ala10-NH2-GnRH) (GnRH-Ant.), 2 mg/kg, on Days 1-15 of life, and killed on Day 48, 56 or 90 of life. The treatment delayed the onset of puberty (monitored by balano-preputial separation) by 8 days (from the age of 48 to 56 days). The weights of testes, seminal vesicles and ventral prostates were reduced by 50-60% on days 48 and 56 of life, but only the testis weights remained suppressed by Day 90. Levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), but not those of prolactin (Prl), were elevated 2-to-4-fold in the treated animals at the three ages studied. Serum and testicular testosterone (T) and the receptors for LH and Prl were suppressed in the peripubertal animals (48 and 56 days), but serum T was elevated and the receptor levels were normal in the 90-day group. The testicular FSH receptors were 50% suppressed at all ages studied. Only minor changes were observed in testicular histology when studied at 48 and 56 days. The 85-day-old animals treated with GnRH-Ant. were infertile when mated with females.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lithium-induced changes in the plasma and pituitary levels of luteinizing hormone,follicle stimulating hormone and prolactin in rats

Adult male Sprague-Dawley rats, maintained under a controlled photoperiod of LD 14:10 (white lights on at 06:00 h, CST), were injected with lithium chloride and changes in the levels of plasma and pituitary homogenates of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were examined to evaluate the effects of this anti-manic drug on reproductive function. Two groups of rats were injected with lithium chloride intraperitoneally, twice daily at 09:00 and 16:00 h, for 2 and 7 days at a dosage of 2.5 meg/Kg body weight. Plasma and pituitary levels of LH, FSH and PRL were measured by radioimmunoassay. Plasma levels of LH were significantly (P<0.05) increased after 2 days of lithium treatment. In contrast, a significant (P<0.005) reduction in plasma levels of LH was evident when lithium injections were continued for 7 days. The plasma levels of FSH remained unaffected by lithium treatment by either time period. Lithium administered for 2 days did not bring about any significant alteration in the plasma levels of PRL, although there was a significant (P<0.002) reduction in plasma PRL levels after 7 days treatment. The concentrations of pituitary LH, FSH and PRL remained unchanged after 2 and 7 days of lithium treatment.     

Diethylstilbestrol increases the density of prolactin cells in male mouse pituitary by inducing proliferation of prolactin cells and transdifferentiation of gonadotropic cells

Diethylstilbestrol (DES) has been implicated in mammalian abnormalities. We examined the effects of DES on follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) cells in the pituitaries of male mice treated with various doses of DES for 20 days. DES reduced the density of FSH and LH cells in a dose-dependent manner, but increased that of PRL cells. When the expression of estrogen receptor (ER) α and β was assessed, an induction of ERβ by DES was found predominantly in PRL cells. However, since these effects were abolished in ERα knockout mice, DES appears to act primarily through ERα. When the expression of Ki-67 and Pit-1 in PRL cells was examined at various time-points after DES treatment, some PRL cells became Ki-67 positive at 10–15 days, and Pit-1-positive cells were increased at 5–15 days. Furthermore, some FSH and LH cells became Pit-1 positive, and co-localized with PRL at 5–10 days. Our results indicate that DES increases PRL cells by inducing proliferation of PRL cells and transdifferentiation of FSH/LH cells to PRL cells.     

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.     

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.     

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.     

Pituitary hormones dependent expression of insulin-like growth factors I and II in the immature hypophysectomized rat testis

Since insulin-like growth factors I (IGF-I) and II (IGF-II) appeared involved in paracrine or autocrine regulation of both cell multiplication and differentiation of the rat testis, we have investigated the pituitary hormonal dependence of IGF-I and IGF-II mRNA production in the testis of immature hypophysectomized rats (22 days old) supplemented with highly purified FSH, LH, GH or PRL. Our data show that testicular expression of IGF-I mRNA as measured by dot-blot hybridization, is increased by LH, FSH or GH treatments of 7-, 6-, and 4-fold, respectively, above controls. Intensity of the signal was 3-fold lower after PRL treatment than in hypophysectomized control rats. On the contrary, IGF-II mRNA expression, was found low in the immature hypophysectomized rat testis and unmodified by any hormonal treatment. In contrast to the increase of IGF-I expression in the testis no significant change in the IGF-I plasma concentration was observed after LH or FSH supplementation. GH treatment, as expected, increased 4-fold the IGF-I plasma concentration of the experimental animals. Since we have previously shown that LH, FSH, and GH exhibit selective cell multiplication and differentiation in the testis of our animal model, it is proposed that testicular IGF-I expression could be the tissue response to pituitary hormone in these phenomena.     

Properties of the binding of follicle-stimulating hormone to the fetal rat testis

Basic properties of the binding of [131I]-labeled rat FSH ([131I]rFSH) to the testicular homogenates of fetal rats were analyzed by micro-radioreceptor assay. Specific binding of FSH was detectable in the testicular preparations from 15.5-day fetuses, but it was very low. After 17.5 days of gestation, specific FSH binding was apparent in the testis and was effectively displaced by rat FSH but not by rat LH. The Scatchard plot analyses of the binding of FSH to the testicular preparations of fetuses showed straight lines similar to those of postnatal rats, suggesting the presence of a single class of binding sites. The mean dissociation constant (Kd) for FSH receptors in 17.5-day fetuses was 0.413 +/- 0.043 nM, which was significantly greater than that in postnatal rats at 50 days of age. However, the Kd in 19.5-day fetuses was not significantly different from those in 17.5-day fetuses and postnatal rats due to its considerable variance. The capacity of FSH binding sites was 0.51 +/- 0.01 fmol/testis in 17.5-day fetuses, which was significantly less than those of 19.5-day fetuses and postnatal rats.     

Placebo-controlled study of effects of epimestrol on the pituitary-testicular axis in normal men

Twenty healthy male volunteers were randomly allocated to the treatment with either 15 mg/day of epimestrol or placebo for 10 days. The plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), oestradiol (E2) and prolactin (PRL) were measured before, during and 4 days after the medication by radioimmunoassays. Data were statistically evaluated by means of an analysis of covariance. Circulating LH and FSH, and also T and E2 significantly increased in the epimestrol treated subjects. In the placebo treated subjects no significant changes in the plasma hormone levels were observed. There were no significant changes in the plasma levels of PRL in either group.     

Hormonal regulation of testicular human chorionic gonadotropin binding and steroidogenesis in adult mice with different forms of hereditary diabetes and obesity

The regulation of testicular hCG binding and steroidogenesis in adult mutant mice with hereditary diabetes and obesity was studied. Low doses of hCG caused no change in hCG binding in obese (ob/ob) mice, whereas, in diabetic (db/db) mice, the increase in binding measured 24 h after hCG administration was not as great as in normal males. Intermediate doses of hCG caused a decrease in hCG binding in obese and normal mice, but not in diabetic animals. However, 72 h after injection of intermediate doses of hCG, a decrease in hCG binding also was observed in diabetic mice. Plasma testosterone was elevated 24 h after hCG injection in all types of mice studied, but the increase in diabetic mice was smaller than in normal animals. However, 72 h after treatment with hCG, plasma testosterone was still elevated in diabetic mice, but not in normal males. In vitro, hCG stimulated testicular testosterone synthesis in all groups of mice, but the observed increase was smaller in diabetic and obese than in normal animals. Plasma LH levels were higher in diabetic than in normal mice, whereas plasma FSH and prolactin levels were lower in obese mice than in normal animals. All parameters (i.e., LH receptors and circulating hormone levels) measured in yellow (Ay/a) mice were similar to those in normal (a/a) mice. The present study indicates that in these models for noninsulin-dependent diabetes, the testicular metabolism of LH receptors and capacity to secrete steroids is altered.     

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)     

Amino-terminal leucine-rich repeats in gonadotropin receptors determine hormone selectivity.

Recombinant expression of truncated receptors for luteinizing hormone/chorionic gonadotropin (LH/CG) revealed that the amino-terminal leucine-rich repeats 1-8 of the extracellular receptor domain bind human chorionic gonadotropin (hCG) with an affinity (Kd = 0.72 +/- 0.2 nM) similar to that of the native LH/CG receptor (Kd = 0.48 +/- 0.05 nM). LH/CG receptor leucine-rich repeats 1-8 were used to replace homologous sequences in the closely related receptor for follicle stimulating hormone (FSH). Cells expressing such chimeric LH/CG-FSH receptors bind hCG and show elevated cylic AMP levels when stimulated by hCG but not by recombinant human FSH (rhFSH). Similarly, a chimeric LH/CG receptor in which leucine-rich repeats 1-11 originated from the FSH receptor is activated by rhFSH but not by hCG. For this chimera, no residual [125I] hCG binding was observed in a range of 2 pM to 10 nM. Our results demonstrate that specificity of gonadotropin receptors is determined by a high affinity hormone binding site formed by the amino-terminal leucine-rich receptor repeats.     

Adenohypophyseal hormone response to chronic stress in dexamethasone-treated rats.

The influence of dexamethasone treatment on the basal values of corticosterone, GH, prolactin (PRL), LH and FSH, as well as on the adenohypophyseal hormone response to chronic stress was studied in female rats. Dexamethasone acetate (25 micrograms/100 b.w.), given by gavage twice daily for 10 days, decreased the resting plasma levels of corticosterone, GH, LH and PRL, whereas the FSH titers remained normal. The secretion of ACTH (evaluated indirectly through corticosterone concentrations) and of GH appeared to be most sensitive to the suppressive effect of dexamethasone. The same hormonal response pattern was induced by 8 h of daily immobilization for 10 days, except that ACTH release was enhanced and the plasma LH titers dropped more drastically. Dexamethasone administration in combination with restraint did not alter the characteristic hormonal profile of chronic stress, despite the fact that ACTH secretion was completely blocked. These data suggest that the inhibition of PRL, LH and GH secretion following severe, chronic stress is not causally related to the sustained elevation of plasma ACTH.     

Pituitary gonadotropins, hypothalamic gonadotropin-releasing hormone, and testicular traits of boars exposed to natural or supplemental lighting during pubertal development

Seventy crossbred boars were reared under natural (30 lux) or supplemental lighting (1000 lux) beginning at 4 wk of age. Boars received supplemental lighting from six 40-watt fluorescent bulbs between 0530 and 2030 h. Five boars from each treatment were killed at 67, 91, 119, 155, 182, 210, or 246 days of age. No differences (p greater than 0.05) in pituitary concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were found between treatment groups at any age. Total pituitary content of LH, FSH and PRL increased as boars became older, but when expressed as hormone concentration, only PRL increased with age. Content of gonadotropin-releasing hormone (GnRH) in the pituitary stalk-median eminence, preoptic area, and hypothalamus proper was similar (p greater than 0.05) between treatments. When GnRH contents were totaled and combined for the treatment groups, it was found that GnRH content increased (p less than 0.05) as boars became older. No differences (p greater than 0.05) were observed in testicular volume percentage of seminiferous tubules and tubular diameter between lighting treatments. These data demonstrate that the supplemental lighting does not influence puberty in boars by altering hypothalamic content of GnRH or pituitary stores of LH, FSH, and PRL.     

Temporal relationship of the prolactin-dependent LH-induced LH receptor to the LH stimulus

The time course for LH induction of luteinizing hormone (LH) receptors as reflected in binding of ¹²⁵l-labeled hCG was investigated in hypophysecto-mized adult male rats. A low dose of oLH (10 μg) was administered to hypophysectomized adult male rats following pretreatments with prolactin, follicle-stimulating hormone (FSH), growth hormone (GH), or saline. Testicular binding of hCG was determined at different times following the LH injection using Leydig cell membrane preparations from a testicular homogenate. Seven days after hypophysectomy, hCG binding was at a nadir of 19 ± 7% (mean ± SD) of control values. Pretreatment with prolactin (100 μg/day) for 7 days was associated with a nonsignificantly different hCG binding that was 30 ± 5% of control values. Prolactin pretreatment plus a single 10 μg LH i.p. injection increased ¹²⁵l hCG binding up to 56 ± 10% of control values within 30 minutes of the LH injection. Luteinizing hormone-induced hCG binding persisted at a high level (51 ± 4% of control values) for 2 hours but returned to hypophysectomized control levels 6 hours after the i.p. LH injection. Seven days pretreatment with FSH or GH at 100 μg/day plus 10-μg LH injections was also tested. Neither FSH nor GH had a statistically significant effect on hCG binding nor could they mimic the ability of prolactin to allow for LH induction of hCG binding in the hypophysectomized adult male rats. These studies suggest that the induction or “up-regulation” of Leydig cell hCG binding by ovine LH is rapid and specifically dependent upon pre-exposure to prolactin.     

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.     

Purification of equine gonadotropins and comparative study of their acid-dissociation and receptor-binding specificity

A method for the simultaneous purification of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from equine pituitaries is briefly described. Different forms of each hormone were obtained. The total yield of LH was 24.2 mg·kg^?1 with a recovery of 22% and the yield of FSH was 26 mg·kg^?1 with a recovery of 34%. The specific activities of both hormones, measured in homologous equine radio-receptor assays are equal to or higher than those of the preparations described so far. In all species studied so far the acid-dissociation curves of LH and FSH are similar; this is an agreement with the view that the binding of the common α-subunit and the specific β-subunits involves polypeptide regions which are identical in both hormones. In contrast, the acid-dissociation pK_a of equine LH was found to be considerably lower (3.9) than that of equine FSH (5.8). The equine gonadotropins exhibit a much lower specificity with receptors of a porcine testicular fraction compared with an equine fraction. Equine LH exhibited a binding activity on FSH receptors from a porcine testicular fraction equal to 20% that of equine FSH instead of only 1% for an equine binding fraction. Similarly, all the equine FSH preparations tested exhibited a five-fold higher binding-activity on porcine LH receptors than on equine LH receptors. In the porcine system, pregnant mare serum gonadotropin behaved like equine LH towards LH and FSH receptors. In contrast, on equine binding fraction, pregnant mare serum gonadotropin was only 4% as active as equine LH and was devoid of FSH activity. All the data we have obtained are consistent with the ‘negative specificity’ model we proposed recently.     

Effect of prolactin and growth hormone on prolactin and LH receptors in the dwarf mouse.

Dwarf mice (DW/J;dw/dw) which exhibit a deficiency of prolactin and GH secretion were treated for 8 days with ovine prolactin and/or human GH (10 or 20 mug/day) and the effect on hepatic and testicular prolactin receptors was investigated. In both sexes there was a significant increase in body weight after all hormone treatments, but an increment in testicular weight was observed only after prolactin administration. Prolactin treatment increased the specific binding % of prolactin in liver membranes in females but not males, and in testicular homogenates (together with an increase in LH receptors). The results suggest that lack of prolactin but not of GH retards sexual development in these mice. Treatment with prolactin partly counteracts this deficiency, and the effect may be mediated by the induction of hepatic and testicular prolactin and LH receptors.