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SUMMARY

In male mice of the C57BL/10J (C57) strain the testicular weight, sex drive and aggression are low compared with a number of other strains, indicating androgen deficiency. In contrast, DBA/2J (DBA) males were 'normal' in all studied parameters of testicular function. The weight of the seminal vesicles is similar in both strains.

Plasma testosterone levels, and the responsiveness of the seminal vesicles to injected testosterone propionate in C57 and DBA animals were compared. Plasma testosterone levels were 1·3 ± 0·4 ng/ml in C57 and 4·6 ± 1·0 ng/ml in DBA mice. The increase in weight of the seminal vesicles after administration of testosterone propionate to castrated male mice was, however, considerably greater in C57 than in DBA mice. In order to restore the weight of the seminal vesicles to normal it was necessary to administer twice as much testosterone propionate to DBA than to C57 males.

The physiological role of prolactin in male mammals is virtually unknown. However, in genetically sterile dwarf mice prolactin was demonstrated to promote male fertility (Bartke, 1966). The possibility of an influence of prolactin on the growth of male accessory sex organs was reported in the rat, the mouse and the guinea-pig (Meites & Nicoll, 1966; Morrison & Johnson, 1966). Seminal vesicles of the male mouse were enlarged by a 'mammotropic' tumour, probably secreting massive amounts of prolactin (Haran-Ghera, 1966). The present work was undertaken to test the effects of a relatively low dose of prolactin from a single pituitary homograft on the weight of the seminal vesicles and penis in castrated laboratory mice.

The mice were from five genetically different strains: three from our colony, Outbred strain, inbred E strain and F ₁ mice from a cross of inbred strains P and E (Krzanowska, 1965) and two from strains brought

SUMMARY

Hypophysectomized mice were treated daily for 28 days with 12 i.u. prolactin, 10 μg luteinizing hormone (LH), 10 μg LH plus 12 i.u. prolactin, 50 μg testosterone propionate (TP), or 50 μg TP plus 12 i.u. prolactin. The yield of spermatogenesis was studied quantitatively from the counts of spermatogonia, preleptotene and pachytene spermatocytes and spermatids in the seminiferous tubules at stage VII of spermatogenesis. Prolactin administered alone caused a small, but significant, increase in the yield of spermatogenesis. Treatment with a mixture of LH, follicle-stimulating hormone and growth hormone in amounts 1·5 times higher than those reported as contaminants of prolactin had similar effects. Injections of LH or TP caused partial restoration of spermatogenesis. The yield of spermatogenesis was significantly higher in animals given LH plus prolactin than in the animals given LH alone. Prolactin, however, did not augment the effects of TP on spermatogenesis. It is concluded that prolactin acts on the Leydig cells of the testis to increase their responsiveness to LH. More androgen appears to be produced under the influence of LH when prolactin is also present.

SUMMARY

In intact adult male mice three injections, 2 h apart, of 3 μg luteinizing hormone (LH), 15 μg LH or 100 μg follicle-stimulating hormone (FSH) decreased the concentration of esterified cholesterol in the testes. Treatment with 35 μg testosterone propionate (TP)/day or 4 mg aminoglutethimide/day increased the concentration of esterified cholesterol. Single heterotopic pituitary homografts increased the concentration of esterified cholesterol; injecting 7·5 i.u. prolactin twice daily had similar effect. The concentration of free cholesterol showed little individual variation and little or no response to any of the above treatments. The concentration of testicular total cholesterol was increased in hypophysectomized mice. Administration of 10 μg LH or 50 μg TP daily for 28 days reduced the concentration of both esterified and free cholesterol in these animals to approximately the levels found in intact adult males. Prolactin (12 i.u./day) given alone or with TP had no effect, but it increased the concentration of esterified cholesterol in LH-treated animals. It is concluded that in the mouse testis the concentration of esterified, but not free, cholesterol tends to fluctuate with the apparent changes in the rate of androgen synthesis and that prolactin promotes accumulation of cholesterol esters. This could explain the synergism between prolactin and LH in stimulating spermatogenesis and the growth of androgen dependent tissues.

The pituitary gland of the male adult rodent contains as much prolactin as that of immature females (Jones, Fisher, Lewis & VanderLaan, 1965), but the significance of its occurrence in the male is not clear. The effect of prolactin on male fertility was therefore studied in genetically dwarf mice (dwarf = dw and Ames dwarf = df).

The adenohypophysis of dwarf mice produces little or no prolactin, even when removed from hypothalamic inhibition (Bartke, 1965b). Female dwarf mice are sterile but can reproduce normally when prolactin is provided (Bartke, 1965a, 1966). In a non-inbred stock of df dwarfs, grafting normal mouse pituitary into the renal capsule increased the proportion of fertile dwarf males. This indicates a role of prolactin in male fertility. However, pituitary grafts, in addition to secreting prolactin, have pronounced growth hormone (GH) and some thyroid-stimulating hormone (TSH) activity (Hertz, 1959) and it is known that both GH

ABSTRACT

In the male rat, hyperprolactinaemia is associated with significant reductions in plasma LH and FSH levels and in several measures of copulatory behaviour. In contrast to this situation, experimental induction of hyperprolactinaemia in male mice and hamsters is associated with an increase in plasma gonadotrophin levels. It was therefore of interest to determine the effects of hyperprolactinaemia on the copulatory behaviour of these animals. Hyperprolactinaemia was induced by transplantation of pituitaries from adult females and sexual behaviour was tested in the presence of ovariectomized, oestrogen- and progesterone-treated females. Because hyperprolactinaemia increases plasma testosterone levels in intact male hamsters, the animals were castrated and implanted with testosterone-filled silicone elastomer capsules before induction of hyperprolactinaemia. In mice of two inbred strains, DBA/2J and C57BL/6Bg, hyperprolactinaemia appeared to stimulate male sexual behaviour as shown by a significant increase in the proportion of animals mating (C57BL/6) and a significant decrease in mount (DBA/2J) and intromission (C57BL/6Bg and DBA/2J) latencies. Similarly, hyperprolactinaemia did not suppress male copulatory behaviour in the hamster. In contrast, in two experiments in which the animals were tested three times for sexual behaviour, mount or intromission latencies were significantly reduced in pituitary-grafted, as compared with sham-operated males, in the first of the tests. Thus, in the mouse and the golden hamster, experimentally induced chronic hyperprolactinaemia stimulates both gonadotrophin release and male copulatory behaviour. These observations, together with the association of suppressive effects of hyperprolactinaemia on plasma LH and FSH levels and on sexual behaviour in the male rat, suggest the possible existence of a common mechanism underlying both endocrine and behavioural effects of hyperprolactinaemia. We suggest that the suspected effects of hyperprolactinaemia on the release of endogenous LHRH in the hypothalamus may represent such a mechanism.

J. Endocr. (1987) 112, 221–228

The effect of increasing gestational age and maternal exposure to cannabinoids on body weight, ano-genital distance and androgen concentration in fetal mice was examined. Body weight increased in both male and female fetuses from days 16 to 18 (the presence of a vaginal plug was considered to indicate day 1 of pregnancy), while ano-genital distances tended to increase faster in male than in female fetuses. The concentration of testosterone increased with age in fetuses of either sex. However, at day 16, there was a significant influence of fetal sex on testosterone concentration with two non-overlapping distributions, one above and one below 300 pg/g fetal tissue, correlating with male and female gender respectively. After day 16, male fetuses tended to have higher testosterone concentrations, but some values obtained in females did overlap.

Treatment of female mice with Δ⁹-tetrahydrocannabinol, the main psychoactive ingredient of marihuana, from days 12 to 16 of pregnancy caused a significant (P < 0·01) increase in fetal deaths in utero. Cannabinol treatment had no effect on this parameter, but reduced body weight (P < 0·02) in female fetuses, and increased ano-genital distance (P < 0·05) in male fetal mice. The concentrations of testosterone and dihydrotestosterone were reduced in male but not in female fetuses.

The results indicate that exposure to psychoactive or non-psychoactive constituents of marihuana suppresses testosterone levels in fetal as well as in immature and adult mice, as we have previously reported. Thus, maternal exposure to cannabinoids may interfere with the process of sexual differentiation in their male offspring as a result of decreased fetal androgen production.

SUMMARY

Increased synthesis de novo of cholesterol by testes of rats and mice was found to be a contributing factor in the increased testicular cholesterol content after hypophysectomy. This was shown by increased [1-¹⁴C]acetate incorporation in vitro into free and esterified cholesterol by testicular tissue from rats and mice hypophysectomized 3 weeks earlier, as compared with intact controls.

In mice, testicular cholesterol content was significantly increased 1 day after hypophysectomy at which time there was no change in the testis weight. Three weeks after the operation there was a significant decrease in testis weight and a significant increase in the concentration of free, esterified and total cholesterol as well as in the percentage of esterified fraction. These changes were even more pronounced 1 month later.

The regulation of binding of ¹²⁵I-labelled human chorionic gonadotrophin (hCG) to testis was studied in mutant mice with congenital deficiency of prolactin (dw/dw), in mice with prolactin deficiency induced by treatment with bromocriptine and in normal untreated mice. After injection of hCG, normal mice showed a dose-related decrease in testicular hCG binding and subsequent recovery from down-regulation, similar to previous findings in the rat. Mice with congenital prolactin deficiency had a similar dose–response curve of receptor loss after hCG administration, but recovered from down-regulation faster than the normal mice. Induction of prolactin deficiency with bromocriptine prevented down-regulation of hCG binding. The differential effects of congenital and drug-induced prolactin deficiency could be related to a difference in the duration of the deficiency or to its severity. However, this difference could also suggest direct effects of the dw mutation and/or bromocriptine on the Leydig cells.

Testicular regression was induced in adult golden hamsters by exposure to a short photoperiod (5 h light: 19 h darkness). The response of these animals to exogenous steroids (ten injections each of 5 mg testosterone, testosterone propionate, pregnenolone, progesterone or cortisol administered s.c. three times/week) was evaluated from weight changes in testes and seminal vesicles, from plasma levels of LH, FSH and testosterone, and from testicular human chorionic gonadotrophin (HCG) binding and testosterone levels. Administration of testosterone or testosterone propionate produced a decrease in plasma gonadotrophins and a three- to fourfold increase in weights of testes and seminal vesicles, thus indicating that the seminiferous tubules, similarly to accessory reproductive glands, retained the ability to respond to androgenic stimulation. Binding of HCG by testicular tissue was dramatically reduced by treatment with testosterone, probably reflecting atrophy of the Leydig cells. Treatment with pregnenolone or progesterone failed to increase testicular weight, seminal vesicle weight or concentrations of testosterone in the testes. This suggests that the atrophic testes of these animals may have a limited capacity to produce biologically significant amounts of androgens from C21 steroids. Administration of cortisol did not alter any of the parameters of reproductive function that were examined.