The effect of luteinizing hormone releasing hormone on the copulatory behavior of hyperprolactinemic male rats.

The present study was undertaken to test the hypothesis that the deficits in copulatory behavior observed in hyperprolactinemic male rats may be related to a reduction in hypothalamic release of luteinizing hormone releasing hormone (LHRH). Adult male Fischer 344 rats were made hyperprolactinemic by ectopic pituitary grafts or were sham operated and 30 min prior to being tested for copulatory performance received a single subcutaneous injection of 500 ng LHRH, 100 ng LHRH, or saline. On different occasions, testosterone (T) levels were measured in plasma collected 30 min following identical treatments. Plasma prolactin (PRL) levels were determined in samples collected 30 min after injection of 500 ng LHRH. Pituitary grafting produced the expected, significant increase in plasma PRL levels and significant deficits in copulatory behavior. Treatment of hyperprolactinemic subjects with 500 ng LHRH significantly reduced both the time to first intromission and the time to ejaculation to times comparable with those of sham-operated subjects. The 100-ng dose produced a significant reduction in mount frequency. Plasma T levels were significantly elevated following either dose of LHRH. These results demonstrate that exogenous LHRH can restore normal copulatory performance in hyperprolactinemic male rats and support the hypothesis that a reduction in hypothalamic LHRH release is responsible for the behavioral deficits observed in those animals.

Effects of hyperprolactinaemia on male sexual behaviour in the golden hamster and mouse.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal exposure to delta 9-tetrahydrocannabinol enhances sexual responses in the adult male mouse.

From day 1 post partum to postnatal day 5, lactating female mice were given daily oral doses of 25 microliters sesame oil, 0.5 mg tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1-ol (delta 9-tetrahydrocannabinol; THC)/kg or 50 mg THC/kg in 25 microliters oil. Additionally, the pups were given 20 microliter oil, 10 micrograms testosterone or 20 micrograms testosterone in 20 microliter oil s.c. from days 1 to 5 of age. This regimen resulted in nine treatment groups. At 60 days of age, all males were castrated and their testes weighed. After castration, each mouse was implanted s.c. with a 5 mm length of testosterone-filled silicone elastomer capsule. When adult they were tested for male copulatory behaviour. Following behavioural testing the animals were bled by cardiac puncture for measurement of plasma testosterone levels, and their hypothalami removed and assayed for dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and LH-releasing hormone (LHRH). In addition, another two groups of pregnant females were given daily oral doses of 0.5 or 50 mg THC/kg or oil during the first 3 or 5 days of lactation. The male pups were either decapitated for collection of trunk blood or homogenized for determination of serum or whole body testosterone concentrations. Neonatal administration of THC altered adult male sexual responses and had no effect on hypothalamic noradrenaline, 5-HT and LHRH concentrations. There were large increases in serum testosterone concentrations in neonates after maternal THC treatment, although these differences were not significant. Additionally, THC did not influence the testosterone content of neonatal tissue or the testosterone concentration of adult plasma. These results suggest strongly that the effect of THC on male sexual responses is not mediated by its effect on adult hypothalamic neurotransmitter concentrations. Some other potential mechanisms are discussed.

The role of postnatal testosterone in the development of sexually dimorphic behaviors in DBA/1Bg mice.

The DBA/1 Y chromosome causes an increment in aggression and pubertal testosterone levels. The purpose of the following experiments was to determine whether pubertal testosterone is necessary for the normal development of both aggression and copulation in males. If it is, then the effect of the DBA/1 Y chromosome may be mediated by its influence on pubertal testosterone. Individuals were either castrated at 30 days of age (CAS30) or sham operated (Sham or CAS50). At 50 days of age, the CAS30 individuals were sham operated and replaced with testosterone, while the CAS50 group was castrated and replaced with the same quantity of testosterone. The shams were sham operated at 50 days of age. CAS30 individuals were less aggressive than the CAS50 group, while they were no less aggressive than the sham operated group. Additionally, no groups differed in male copulatory behaviors. The results are discussed in relation to Y chromosomal and developmental mechanisms of sexually dimorphic behaviors.

Adrenalectomy does not prevent the hyperprolactinemic, induced sexual behavior deficits in CDF male rats.

Inbred male CDF rats were bilaterally adrenalectomized and received either two pituitaries under each kidney capsule or were sham operated. They were tested at approximately four, seven and eight weeks after surgery. Between the first and second behavioral test, the animals received corticosterone replacement therapy. In each of the three tests, grafted animals exhibited deficits in male sexual behavior as compared to sham-grafted controls. These results suggest that, at least in CDF inbred rats, the adrenal gland is not necessary for the reduction in male sex behavior resulting from chronic hyperprolactinemia.

Suppression of male copulatory behavior by delta 9-THC is not dependent on changes in plasma testosterone or hypothalamic dopamine or serotonin content.

Castrated B6D2 F1 male mice were tested for their sexual responses after being administered 0.5 mg/kg delta 9-tetrahydrocannabinol (THC) 50 mg/kg THC or oil. The animals that received 50 mg/kg, but not 0.5 mg/kg THC, showed deficits in copulatory behavior. Another group of B6D2 F1 castrates were given testosterone propionate (TP) replacement therapy plus 50 mg/kg THC or oil. Similarly, those mice which received 50 mg/kg THC showed behavioral deficits. Lastly, a group of intact B6D2 F1 males were treated with 0.5 mg/kg THC, 50 mg/kg THC or oil, were bled and decapitated, and their brains removed 10 min or 4 hr after treatment. Plasma testosterone (T) and hypothalamic dopamine (DA) levels were unaltered 4 hr after treatment with 50 mg/kg THC, but the concentration of serotonin (5-HT) in their hypothalami was elevated. This effect of THC on hypothalamic 5-HT concentration was not apparent in a larger group of randomly bred animals that were tested. These data strongly suggest that THC's behavioral effects are not mediated by variations in T levels, or by changes in hypothalamic 5-HT or DA concentrations.

The DBA/1Bg and DBA/2Bg Y chromosomes compared for their effects on male sexual behavior.

Mount, intromission, and ejaculation number and latency were measured in male mice of the DBA/1Bg, DBA/2Bg, and DBA/2.DBA/1-YBg congenic strains. The DBA/2 and DBA/2.DBA/1-Y congenic strains differ in the source of their Y chromosome. Fifty percent of the DBA/2 and 13 percent of the DBA/2.DBA/1-Y males mounted at least once in the test of male copulatory behavior. There were no other significant differences between these two congenic strains. This finding suggests that the Y chromosome has an effect on the proportion of mice that mount in this test.

The genetics of hormonal influences on male sexual behavior of mice and rats.

This review focuses on the intersection of genes and hormones as they relate to the development of male sexual behavior. Three major hypotheses are discussed: (1) Some differences in adult male sexual behavior are due to gene differences that influence brain differentiation. Genes that influence brain differentiation may do so by affecting the elaboration of testosterone (i.e., H-Y antigen) or the sensitivity to testosterone (i.e., Tfm mutation and autosomal variations) during neonatal and/or prenatal life. (2) Some differences in male sexual behavior are due to gene differences that influence adult levels of testosterone or sensitivity to testosterone and its metabolites. (3) There is a gene(s) on the Y chromosome that influences the development of sexual behavior that is associated with the arousal mechanism. A possible hormonal mechanism of this Y chromosomal gene(s) is discussed.