Prolactin receptors in the hypoprolactinemic male rat (IPL nude rat): measurement in testis and induction in liver

In order to evaluate the importance of PRL in the regulation of its own receptors, characteristics of specific binding for PRL were studied in membrane preparations from liver and testis of a new hypoprolactinemic male rat, the IPL nude male rat, and this was compared to those found for normal male rats. Under basal conditions, hepatic specific binding of PRL in IPL nude rats, as in normal rats was not detectable. Following castration, it became detectable in both groups, and was 6.99 +/- 0.78% and 6.34 +/- 0.87% for IPL nude and normal rats respectively. Under such conditions, the apparent affinity constant (Ka) and the binding capacity (Nmax) obtained were also similar for both groups (Ka) = 1.36 +/- 0.14.10(9) M-1, Nmax = 102 +/- 14 fmol/mg protein in IPL and Ka = 1.34 +/- 0.28.10(9) M-1, Nmax = 97 +/- 11 fmol/mg protein in normal rats) although a decrease in serum levels of PRL was observed in both groups. This decrease was greater for IPL nude rats. As already reported, estradiol injection following castration was able to further increase the percentage of PRL hepatic specific binding (4 times). Furthermore, our results demonstrated that the affinity constant was significantly increased by estradiol injection in both groups. On the other hand, for testicular PRL binding characteristics, a statistically significant difference was found between IPL nude and normal rats. The PRL specific binding percentage was 7.01 +/- 0.85% for the IPL nude rat and 10.07 +/- 0.64% for the normal rat. By Scatchard analysis, the Ka of testicular membranes for labelled oPRL was similar in both groups, while the capacity differed (Nmax = 9.82 +/- 1.25 fmol/mg protein for IPL nude rat and Nmax = 26.06 +/- 4.39 fmol/mg protein for normal rats). These data established the fact that IPL nude male rats presented characteristics of hepatic PRL receptors similar to those of normal rats, while their testicular oPRL binding significantly differed. These findings therefore suggest that in genetic hypoprolactinemic rats (IPL nude rats), PRL might be more involved in the regulation of testicular PRL receptors than in that of hepatic receptors.     

Steroid regulation of gonadotropins in genetically hypoprolactinemic females (IPL nude rats)

IPL nude females present an absence of lactation with hypoprolactinemia. While males present a slight but significant decrease in serum testosterone and gonadotropins, females show normal values of estradiol, progesterone, LH and FSH during all estrus cycle stages. In this work, we observed that the postovariectomy rise of LH and FSH was significantly lower in the IPL nude females. We studied also the effect of acute (1 injection of 25 micrograms/rat E2Bz) or long-term (E2Bz capsule for 8 days) estradiol benzoate (E2Bz) treatment, with or without progesterone injection (5 mg/rat) in ovariectomized (OVX) IPL and normal females. The sensitivity of gonadotropins to E2 negative feedback is decreased in the IPL nude rats, result in agreement with previous reports and which could be linked to both hypoprolactinemia and decreased beta-endorphin observed in the IPL nude rat. The responsiveness of LH to LHRH was also tested in OVX and OVX + E2Bz or OVX + E2B + P treated. In OVX females responsiveness of LH to LHRH was similar in IPL nude to that of normal females. However, LH responsiveness in acute and long-term steroid-treated OVX IPL nude was significantly depressed. Since the mechanism whereby PRL interacts with steroids to modify gonadotropin secretion is still unexplained, IPL nude rat could be a good model to study it.     

Relationship between bioassay and radioimmunoassay measurement of prolactin in the IPL rat, a hypoprolactinemic rat strain

IPL (Institut Pasteur, Lyon) nude, hypoprolactinemic rats exhibit delayed puberty and a complete lack of lactation. To characterize the secretion of circulating forms of prolactin (PRL) of these rats, PRL concentrations were measured in serum and pituitaries of males and females under various physiological conditions. Two assay methods, a radioimmunoassay (RIA) and a sensitive bioassay (NB2BA) were employed. Normal rats of the Sprague-Dawley strain were tested simultaneously, as controls. The pituitary content of PRL, estimated either by RIA or by NB2BA, in IPL nude males and females was similar to that of normal male and female rats. On the contrary, serum PRL levels of IPL male rats, measured by RIA or NB2BA, were significantly reduced when compared to normal rats. In both groups, there was a close correlation between the results obtained by the two methods, the NB2BA estimates being higher. However, the NB2BA/RIA ratio was significantly decreased in serum from IPL nude rats compared to controls, indicating that the circulating form of PRL was less bioactive in this group. Castrated male rats injected with estradiol showed sharply increased PRL values as estimated by RIA or NB2BA. The increase was greater (35-fold) in IPL nude rats then in normal rats (9-fold), but these increases resulted in serum PRL levels being similar in the two groups. However, the NB2BA/RIA ratio remained significantly reduced in IPL nude rats. In female rats, PRL was measured during different physiological states: estrus, diestrus, proestrus at 1000, 1200, and 1600 h and Days 1 and 21 of gestation and 2 days postpartum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Beta-endorphin in genetically hypoprolactinemic rat: IPL nude rat

Beta-endorphin has been reported to regulate not only stress- and suckling induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, we measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation : IPL nude rat.Beta-endorphin was measured using a specific anti-h-β endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extract from male rats showed greater immunoactivity eluting as I¹²⁵ h-beta-endorphin than in normal rat; this was not the case for the female rat.These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin.     

Prolactin receptor regulation by LH in the rat mammary gland

The aim of this study was to investigate hormonal factors responsible for the huge increase in PRL receptors on the day of estrus in the rat mammary gland. For this purpose, ovariectomized rats were primed with E2 so as to reach a physiological serum concentration of E2 (21.5 +/- 1.2 pg/ml) and high PRL serum values (72.8 +/- 21.9 ng/ml). In these conditions, PRL specific binding and capacity were respectively 22.8 +/- 8.3%/mg protein and 96 +/- 29 fm/mg protein. An injection of either LHRH (500 ng/rat) or LH (60 micrograms LH-RP1/rat) was capable of increasing significantly both PRL specific binding and capacity. Capacity reached the values of 498 +/- 103 and 507 +/- 240 fm/mg protein for LHRH and LH respectively. LHRH action appeared to be mainly mediated through LH secretion, since no difference was found between LHRH and LH. LHRH and LH injections alone were unable to modify PRL binding, suggesting that they only potentiate E2 and PRL action. These results show for the first time that LH is involved in the regulation of PRL receptors in the rat mammary gland.     

The influence of testosterone administration on plasma prolactin levels in the neonatally androgenized (NA) female rat

Neonatally androgenized (NA) female rats were ovariectomized (OVX) as adults and given 1 mg of testosterone propionate/day for 7 days and the plasma prolactin (PRL) pattern compared with NA intact animals and normal OVX animals given estrogen or TP. NA intact animals had elevated basal (morning values) and an attenuated afternoon surge when compared to normal estrogen-treated animals. Testosterone administration to normal animals induced an afternoon surge similar to that of normal estrogen-treated animals but the magnitude of the surge was less. Testosterone given to NA-OVX animals had little effect on either morning or afternoon PRL levels. The results suggest that in the NA rat the brain region involved in the conversion of testosterone to estrogen may be altered by neonatal androgen exposure.     

Paramethasone acetate (PA): corticosteroid potency vs hypothalamic pituitary-gonadal axis

Because paramethasone acetate (PA) suppresses basal and midcycle LH surge and blocks estrogen synthesis in the female, its possible effect upon testicular physiology was evaluated in 13 healthy men by measuring the circulating levels of FSH, LH, prolactin (PRL), testosterone (T), dihydrotestosterone (DHT), androstenedione (A), estradiol (E2) and cortisol (C) every 4 h throughout the day, before (control) and after PA (6 mg/d/7 d). The total concentrations of each hormone, as well as the PA-induced suppressibility (measured as percent decrease in the mean 24 h plasma level) were analyzed. PA suppressed neither the basal nor circadian rhythm of T and had no effect on LH, FSH or PRL output. DHT, A, E2 were significantly reduced and the basal concentrations and circadian variations of C were abolished. PA showed a dual control on the pituitary gonadal axis and while causing a maximal suppressed adrenocortical activity it had no interference in testosterone synthesis.     

Effects of hyperprolactinemia on rat prostate growth: evidence of androgeno-dependence

The effects of the polypeptide hormone prolactin (PRL) in the development and regulation of benign prostate hyperplasia (BPH) and also in prostate cancer are not very well characterized. This study examines the action of PRL, either alone or in association with androgens [testosterone (T) or dihydrotestosterone (DHT)], in the rat prostate gland. The effects of PRL and androgens were investigated after 30 and 60 days in control, castrated, castrated with a substitutive implant of T or DHT, and sham-operated Wistar rats. To enhance PRL release, we induced hyperprolactinemia by administering chronic injections of sulpiride (40 mg. kg(-1). day(-1)). Chronic hyperprolactinemia induces enlargement and inflammation of the lateral rat prostate without any histological changes on ventral and dorsal lobes. We also demonstrate that hyperprolactinemia induces Bcl-2 overexpression in the lateral rat prostate and that this could inhibit the level of apoptosis. The in vivo model established here is a useful in vivo approach for studying the hormonal regulation of normal and pathological prostate development.     

褪黑素通过减弱催乳素基因增强子的突变抑制大鼠垂体催乳素瘤的增生

本工作旨在探讨褪黑素(melatonin,MLT)抑制17-β-雌二醇(17-β-estradiol,E2)诱发的Sprague-Dawley大鼠垂体催乳素(prolactin,PRL)瘤增生的分子机制。结果表明,每只大鼠每日定时皮下注射一定剂量的MLT(0.25、0.50mg)能显著抑制E2诱发的大鼠垂体PRL瘤的增生;偏低(0.05mg)或过高剂量(1.00、2.00mg)的MLT也抑制PRL瘤的增生,但无统计学意义。采用PCR和DNA直接测序显示,与正常垂体对照组比较,PRL瘤中PRL基因增强子出现五处突变,-1885bp位点由C突变为G,-1857~-1855由ACA替换为G,-1792~-1791插入G,-1383~-1382插入GGTGTGTG片段,-1265~-1250缺失GTGTGTGTGTGTGTGT片段。0.25mg/dMLT处理组,PRL瘤中的PRL基因增强子上述个别突变部位仍然存在(-1885由C突变为G),突变消失(-1792~-1791无插入G),大部分表现为突变减弱(-1856~-1855缺失AC,-1385~-1384缺失TG,-1250~-1253缺失GTGT)。采用荧光素酶报告基因检测PRL基因增强子活性显示,正常垂体、PRL瘤和0.25mg/dMLT处理的PRL瘤三组中,PRL基因增强子的活性分别为(13448.17±3012.74)、(161831.67±60996.01)和(10212.17±2634.71)OD单位。PRL瘤组增强子活性较正常垂体升高11倍(P<0.001),MLT处理组增强子活性较PRL瘤组降低93.69%(P<0.001)。上述三组PRL基因增强子空间结构的分析表明,PRL基因增强子DNA的曲折程度为PRL瘤组>MLT处理组>正常垂体。以上结果证实,MLT抑制大鼠垂体PRL瘤增生的重要分子机制之一可能是减弱PRL基因增强子的突变,也提示MLT可减弱PRL基因增强子的突变,从而下调PRL基因的高表达,可能与降低DNA的曲折程度有关。     

Ornithine decarboxylase activity as a marker of androgen and antiandrogen action in the rat epididymis

After castration, there was a marked decrease in serum androgen concentration at 6 h, and a dramatic inhibition of ornithine decarboxylase (ODC) at 12 h. Administration of testosterone propionate to castrated rats at a dose of 0.05 mg/animal restored ODC activity to the normal value. However, no change was observed when intact rats were treated with testosterone even at a 40-fold higher dose, indicating that endogenous androgens present in intact rats are far in excess for maintenance of maximal levels of activity. Administration of the antiandrogen flutamide to intact rats caused a moderate decrease in epididymal weight, whereas this effect was more pronounced in castrated, androgen-treated rats. In the latter, the effect of flutamide was significant at the lowest dose used (0.5 mg/day). ODC activity was significantly decreased by flutamide treatment of intact rats, but even at the highest dose used (10 mg/day) only a 39% inhibition was observed. In flutamide-treated rats, LH concentrations were markedly increased, as were serum and epididymal androgens. In androgen-treated castrated rats, flutamide caused epididymal ODC to fall to undetectable values. These results show that: (1) androgens are essential for the maintenance of ODC activity in the epididymis; (2) epididymal ODC activity is maximally stimulated by endogenous androgens, at least in the pubertal rat; (3) the apparent potency of flutamide is substantially lowered by an increase in epididymal androgens. We suggest that ODC is a sensitive marker of the action of androgens and antiandrogens in the epididymis.     

Androgen metabolism by rat epididymis. 3. Effect of castration and anti-androgens.

The in vivo and in vitro metabolism of 3H-testosterone by rat epididymis and the changes in epididymal weight have been studied after castration and treatment with anti-androgens. The utilization of 3H-testosterone was greatly reduced after castration as was the formation of 5alpha-reduced 17 beta-hydroxy metabolites. The formation of the 17 -keto metabolites was unaffected. Castration had no effect on the ratio between water and ether soluble radioactivity. Administration of testosterone propionate, necessary for giving normal stimulated prostate weight (150 mug/day), restored the metabolism of testosterone to approximately normal values. Estradiol benzoate and progesterone inhibited metabolism of testosterone in vitro and greatly reduced the formation of DHT (17 beta-hydroxy-5alpha-androstan-3-one) and 3 alpha-diol(5 alpha-androstane-3 alpha-17 beta-diol) by experiments both in vivo and in vitro. No effect of cyproterone acetate could be demonstrated on either the in vitro or in vivo metabolism of testosterone. Castration for 14 days reduced the epididymal weight to about 30% of that found in intact animals. Administration of testosterone propionate restored the epididymal weight to about 80% of normal. Estradiol benzoate and cyproterone acetate given to intact rats led to a decrease in the epididymal weight. Progesterone had no such effect. In 14 days castrated rats receiving testosterone propionate all three anti-androgens reduced the weight of the epididymis. In conclusion, our results show that the metabolic conversion of testosterone in epididymis to DHT and 3 alpha-diol is dramatically dependent on the hormonal status of the animal; castration or treatment with anti-androgens causes a reduced formation of the "active" androgens whilst testosterone replacement treatment restores the metabolism of testosterone to normal.     

褪黑素抑制雌二醇诱致的垂体PRL瘤生长与血浆PRL和过氧化脂质含量的关系

雄性大鼠皮下埋置17-β雌二醇(17-β-estradiol,E2)药泵诱发垂体催乳素PRL)瘤,并每日皮下注射褪黑素(melatonin,MLT)观察MLT对E2诱发PRL瘤生长的影响.另外,采用放免法和紫外分光光度法测定大鼠血浆PRL和过氧化脂质(peroxidativelipid,PL)浓度,观察PRL瘤重量与大鼠血浆浓度间的相关关系.实验结果显示,在对照组、0.05、0.25、0.50、1.00和2.00mgMLT组,PRL瘤重量分别为115.0±71.0、85.2±41.0、58.9±24.1、72.7±23.6、79.3±56.1、74.5±46.8mg;血浆PRL浓度分别为493.46±33.3、373.78±26.5、125.13±13.3、201.79±11.2、418.88±41.3、281.94±36.4ng/ml;血浆PL水平分别为1.21±0.23、0.89±0.32、0.92±0.27、0.64±0.24、0.41±0.14、0.43±0.21△D233/ml.相关性分析表明,PRL瘤重量与血浆PRL浓度间的相关系数为0.8738(P＜0.05),与血浆PL水平间的相关系数为0.5550(P＞0.05),血浆PRL浓度与血浆PL水平间的相关系数为0.2141(P＞0.05).该结果提示,(1)0.25(P＜0.01)、0.50(P＜0.05)mgMLT能有效抑制E2诱致的PRL瘤生长和PRL分泌,所有剂量的MLT均能抑制血浆PL的形成;(2)PRL瘤重量与血浆PRL浓度间呈正相关关系,PRL瘤重量与血浆PL水平间、以及血浆PRL浓度与血浆PL水平间均无相关关系.因此,我们认为,MLT抑制E2诱致的PRL瘤生长可能与MLT抑制PRL表达性分泌有关,但与MLT抗氧化作用无关.     

Effect of prolonged incubation of male rat whole pituitary or pituitary-hypothalamus complex with testosterone on release of gonadotrophin and prolactin in vitro.

Investigations were undertaken to study the effect of in vitro addition of testosterone (0.3 mM) on the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) by pituitary-hypothalamus complex (PHC) or the whole pituitary (PI) incubated for 72 hr, with incubation media changed every 24 hr. PHC or PI were from adult intact or castrated (7 days post castration) rats. The tissues incubated with or without testosterone were further exposed to 0.1 nM luteinizing hormone-releasing hormone (LHRH) for 4 hr. Incubation media and the pituitary were analyzed for PRL and gonadotrophin content. While PHC from normal and castrated rats released increasing amounts of LH with diminishing amounts of FSH and PRL at different periods of incubation, PI showed a decrease in the amounts of gonadotrophin and PRL released. Co-incubation of PHC or PI of intact or castrated rats with testosterone stimulated the release of LH and FSH during the first or second-24 hr incubation but inhibited the release of PRL in all the three incubations of 24 hr each. The extent of PRL inhibition increased with increasing incubation period. Testosterone had no effect on LHRH induced release of PRL but inhibited LHRH induced release of LH and FSH by pituitaries from constructs of normal rats. Testosterone reduced intrapituitary contents of PRL and FSH of intact and castrated rats. The data are interpreted to suggest that hypothalamus is essential for the maintenance of functional pituitary in vitro and that intrinsic differences exist in mechanisms regulating the secretion of LH, FSH and PRL.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uterotropic action of indomethacin on the rat uterus

Administration of indomethacin (10 mg/kg body weight, twice daily for 6 days) resulted in a significant (P less than 0.01) increase in the weight, and cross-sectional area of uteri of ovariectomized rats, whereas no such effects were observed following indomethacin administration to normal cycling rats. Prostaglandin F2 alpha (PGF2 alpha) content (ng/uterus) and concentration (ng/g wet weight) in the uterus of indomethacin-treated animals were reduced 40.4% and 60.8%. Simultaneous administration of either estradiol-17 beta (E2), progesterone testosterone with indomethacin to ovariectomized rats failed to reduce the uterine weight increase. On the contrary, concomitant administration of E2 (25 or 100 ng/day) and indomethacin resulted in uterine weight increases which were greater than those associated with indomethacin alone. Uterine E2 content was significantly higher in animals treated with indomethacin plus E2 as compared to those given estradiol alone. Uterine uptake of 2,4,6,7-[3H]E2 following i.v. administration was greater in animals pretreated with indomethacin (5 mg/kg, twice daily) for 3 days than in ovariectomized controls. These results suggest that prostaglandins may be involved in the regulation of uterine growth.     

Estrogen-like effects of 7,12-dimethylbenz(a)anthracene on the female rat hypothalamo-pituitary axis

We have recently demonstrated that 7,12-dimethylbenz(a)anthracene (DMBA), a potent inducer of mammary tumors in rodents, can in vitro decrease the number of membrane dopamine D2 receptors and stimulate prolactin (PRL) release, by direct estrogen-like actions on anterior pituitary. In the present study, we tested the ability of DMBA to mimic the in vivo estradiol (17 beta E2) effects on pituitary D2 receptors and on PRL as well as LH release. We have found that DMBA, like 17 beta E2, when injected to ovariectomized rats, induced a decrease in the number of anterior pituitary D2 receptors, a release of PRL and exerted a biphasic (acute negative and longer term positive) action on LH secretion. We thus examined the ability of DMBA to interact with 17 beta E2 receptors in the hypothalamo-pituitary axis: DMBA binds to the pituitary cytosolic estrogen receptors with an affinity 0.001% that of 17 beta E2. Finally [3H]DMBA binds to hypothalamus-containing brain sections. This binding was displaced partially by RU 2858 a pure estrogen agonist and totally by tamoxifen, a purported estrogen antagonist. No competition for [3H]DMBA binding was observed with an androgen (RU 1881) or a glucocorticoid (RU 26988) agonist. From these data, it may be concluded that DMBA can act as a partial estrogen in pituitary and hypothalamic tissues.     

Influence of bupropion HCl (Wellbatrin), a novel antidepressant, on plasma levels of prolactin and growth hormone in man and rat.

Bupropion HCl (Wellbatrin®), a non-tricyclic compound with antidepressant effects in man, was evaluated for effects on plasma prolactin (PRL) and growth hormone (GH) levels in normal human subjects, and for effects on plasma PRL levels in a series of pharmacological studies in normal rats. Single oral doses of 50, 100 or 200 mg of bupropion given to male (n=6) and female (n=12) subjects produced a marked suppression (80% decrease) of PRL. Incomplete PRL recovery was observed at the end of 24 hours. One hour after drug administration there was a +0.56 correlation of percent decrease in PRL levels with bupropion plasma levels. GH showed only small and erratic changes in plasma levels at 1–4 hours post-dose. In the rat, single bupropion doses of 25 mg/kg, i.p., failed to lower basal PRL levels. Bupropion, however, significantly decreased PRL in rats in which plasma PRL was elevated by pretreatment with alphamethyltyrosine, 5-hydroxytryptophan or quipazine. Bupropion, on the other hand, did not counteract the PRL-elevating effect of haloperidol. Results in man and rat are consistent with the view that bupropion has significant dopamine mimetic properties. Whether bupropion is a direct dopamine receptor-stimulator or an indirectly acting agonist cannot be determined from the present results.     

Characteristics of flutamide action on prostatic and testicular functions in the rat

The effect of daily treatment with the pure antiandrogen Flutamide has been studied either alone or in combination with the LHRH agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide (LHRH-A), on testicular and prostatic functions in adult male rats. Treatment for 10 days with Flutamide (5 mg/rat, twice daily) caused a marked stimulation of plasma testosterone (T) associated with a significant increase in plasma gonadotropin concentrations and inhibited plasma PRL levels. Testicular weight is not changed following antiandrogen administration but testicular LH/hCG receptor levels are markedly decreased with no change in FSH receptor levels. Moreover, Flutamide treatment alone produces an important inhibition of ventral prostate and seminal vesicle weights associated with a significant decrease in prostatic beta-adrenergic receptor levels but no change is observed in specific ornithine decarboxylase (ODC) activity. Daily LHRH-A treatment at the dose of 1 microgram/day for 10 days decreases plasma T to levels comparable to those found in orchiectomized men (0.30 +/- 0.5 ng/ml). This effect is associated with an almost complete loss of testicular LH/hCG receptors, a decrease in testicular weight, a significant increase in plasma gonadotropins and a marked inhibition of plasma PRL concentration. A relatively smaller inhibition of ventral prostate and seminal vesicle weights follows treatment with the LHRH agonist alone, this effect being accompanied by a significant reduction in beta-adrenergic receptor concentration but no change in prostatic ODC activity. Combination of the two drugs, however, caused a potent inhibitory effect on both ventral prostate and seminal vesicle weight to values similar to those found in castrated rats. The prostatic weight loss is accompanied by a marked fall in ODC activity and in the concentration of beta-adrenergic receptors. The present data clearly show that combined treatment with an LHRH agonist and a pure antiandrogen is highly effective in inhibiting, not only prostatic growth, but also two androgen-sensitive parameters of prostatic activity.     

Evaluation of a peripherally selective antiandrogen (Casodex) as a tool for studying the relationship between testosterone and spermatogenesis in the rat.

The endocrine profile and the effects on spermatogenesis of the new antiandrogen, Casodex [2RS)-4-cyano-3-(4-fluorophenylsulphonyl)-2-anilide, CAS) were evaluated in the adult rat. In the first experiment rats were administered CAS at daily doses of 10, 20 and 40 mg/kg for 14 days. For comparison groups receiving flutamide (FL, 10 mg/kg) and ethane dimethane sulphonate (EDS) were included. Unlike FL, administration of CAS (10 and 20 mg/kg) did not significantly raise serum concentrations of gonadotropic hormones and testosterone. With 40 mg/kg CAS gonadotropin secretion, but not testosterone levels, were elevated on day 15. Administration of CAS lowered the weight of the seminal vesicles and coagulating glands comparable to the administration of the Leydig cell toxin EDS. In contrast to FL a significant loss of germ cells in stage VII of spermatogenesis was observed with CAS. In a second experiment the ability of FL and CAS to block testicular androgen action was compared in rats with reduced testicular androgen production induced by a gonadotropin-releasing hormone antagonist. Both antiandrogens markedly enhanced spermatogenic involution as revealed by quantitative flow cytometric analysis of germ cell numbers. The study demonstrates that (a) CAS is a peripherally selective antiandrogen and (b) CAS might provide a feasible approach to study androgen dependence of spermatogenesis in the presence of normal FSH levels.     

Hyperprolactinemia and sexual function in men

Male hyperprolactinemia (HPRL) is known to induce different types of sexual dysfunctions. In order to determine the incidence of HPRL among patients referred for sexual dysfunction, serum prolactin (PRL) was assayed in 1053 clinically idiopathic cases. Among 850 cases complaining of erectile impotence, 10 with marked HPRL (1.1%, PRL above 35 ng/ml) were found, of whom 6 cases were associated with a pituitary adenoma. 17 mild HPRL (2%, PRL 20-35 ng/ml) were also found. Among 124 cases with premature ejaculation, 13 (10%) mild HPRL were found. Serum PRL was normal in 51 cases complaining of an ejaculation without orgasm, and 27 patients exclusively complaining of reduced sexual desire. Our results lay stress on the fact that serum PRL must be assayed in every case of clinically idiopathic erectile impotence. Indeed, 5 of the 10 marked HPRL patients would have been misdiagnosed if we had only assayed this hormone when plasma testosterone was below the normal range. Moreover, in order to shed some light on the mechanisms by which HPRL disturbs male sexual function, the sexual behaviour of 17 markedly HPRL males was compared to their serum levels of PRL and testosterone, first before treatment, then at regular intervals during treatment. Our main conclusion is that impotence cannot be totally explained by a decrease in plasma testosterone, because this steroid hormone was within the normal range 7 of the 16 impotent patients. Moreover, when serum PRL was lowered by bromocriptine, 6 patients recovered their potency before plasma testosterone clearly increased, and in 3 of those patients before it reached the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)