Nicholas R. Hall

Differential effectiveness of testosterone and its metabolites in the induction of male sexual behavior in two strains of albino mice

Abstract The present series of studies examined the relative effectiveness of the four naturally occurring androgens testosterone, androstenedione, dihydrotestosterone, and androstanedione to induce male sexual behavior in castrate CD-1 and Swiss-Webster (SW) mice. Testosterone treatment resulted in the display of sexual behavior in both strains, but it was clearly more effective in the SW strain in which a higher percentage of males displayed intromissions and ejaculations than in the CD-1 strain. Dihydrotestosterone had essentially no behavioral effects in the CD-1 strain, while it was only slightly less potent than testosterone in the SW strain. Although less potent than either dihydrotestosterone or testosterone, androstenedione treatment also resulted in the display of mating behavior in some of the SW males and in an even fewer number of the CD-1 males. Androstanedione treatment failed to induce mating behavior in either strain. Testosterone, dihydrotestosterone, and androstenedione were all found to stimulate moderate seminal vesicle and penile growth whereas androstanedione was only weakly effective in these somatic measures. These results were compared and contrasted with earlier findings on the androgenic control of agonistic behavior in the mouse, sexual behavior in the rat, and perinatal neural sexual differentiation in both the rat and mouse. The results from all of these studies were interpreted to support the hypothesis that different androgen metabolites are differentially effective in different target tissues and in the induction of different behaviors. It was further pointed out that these effects are both strain and species dependent.

Androgen-induced agonistic behavior in castrate male Swiss-Webster mice: comparison of four naturally occurring androgens.

Agonistic behaviors including tail rattling, biting and fighting between castrate male Swiss-Webster mice living in isolation and group-housed castrate male SW mice was facilitated by treatment with testosterone, dihydrotestosterone or androstenedione. In these tests testosterone appeared to be more potent than dihydrotestosterone and androstenedione. These three androgens as well as androstanedione were all capable of stimulating growth of the seminal vesicles and preputial glands. As potency in these peripheral tissues did not parallel potency in the behavioral tests it was suggested that different hormone metabolites are differentially effective in different target tissues and in different behaviors. Differences between these data and similar data for the CD-1 mouse were also discussed.

Stimulation of male and female sexual behavior in gonadectomized rats with estrogen and androgen therapy and its inhibition with concurrent anti-hormone therapy ☆

In the first experiment gonadectomized male rats were injected daily with various combinations of vehicle (V), estradiol benzoate (E), dihydrotestosterone (D) and/or the anti-androgen cyproterone acetate (CA). The eight treatment combinations consisted of V, E, D, CA, E + D, E + CA, D + CA and E + D + CA. Only those males treated with both E and D were found to display ejaculations. Concurrent treatment with CA completely blocked ejaculatory behavior and it significantly reduced both mount and intromission frequencies. Examination of peripheral androgen target tissues indicated that following stimulation with D, CA effectively reduced seminal vesicle and penile weights, and penile lengths, but it did not reduce penile spines. In the second experiment gonadectomized female rats were treated with two daily injections of E, E + CA or E + the anti-estrogen CI-628. A second set of gonadectomized females received three daily injections of testosterone (T), T + CA or T + CI-628. On the day after completion of these injections all females received progesterone and were tested for sexual receptivity three hours later. Both E and T treated females were found to display the lordotic posture in response to mounting stimulation while both CI-628 and CA were found to block this behavior. In E treated females, CI-628 and CA were also found to reduce uterine weight. Thus, CA was shown to have anti-estrogenic as well as anti-androgenic properties. These results were discussed in terms of the aromatization and 5alpha reduction theories of testosterone action in sexual behavior.

Studies on the neuroendocrine, somatic and behavioral effectiveness of testosterone and its 5α reduced metabolites in Swiss-Webster mice ☆

Abstract In this series of studies we examined the relative potency of testosterone and three of its 5α reduced metabolites using Swiss-Webster mice. Dihydrotestosterone and 3α-androstanediol were found to be more potent in feedback suppression of gonadotropin secretion than testosterone and 3β-androstanediol as assessed by inhibition of ovarian compensatory hypertrophy and by production of testicular atrophy. All four of these androgens were potent stimulators of seminal vesicle growth with dihydrotestosterone > 3 α -androstanedione > 3 β -androstanediol > testosterone. When dissolved in propylene glycol vehicle testosterone was by far the most effective stimulator of male sexual behavior, followed by 3β-androstanediol and finally 3α-androstanediol. Dihydrotestosterone failed to stimulate sexual behavior when dissolved in this vehicle; however, when dissolved in an oily vehicle dihydrotestosterone was nearly as potent as testosterone.

Intracerebral prostaglandin E2: Effects upon sexual behavior, open field activity and body temperature in ovariectomized female rats

A single 27 gauge implant of PGE2 into the periventricular region of the hypothalamus resulted in a significant increase in sexual receptivity in estrogen primed, ovariectomized female rats. Open field activity levels were only slightly decreased while rectal body temperature increased significantly over control values. It is postulated that the effects upon sexual receptivity might be mediated by PGE2 stimulated LRF release.

Effects of pre- and post-treatment with unlabeled steroids on thein vivo uptake of [3H]progestins in selected brain regions, uterus and plasma of the female mouse

The levels of ethyl acetate extractable radioactivity retained in various brain samples and in the uterus and plasma of ovariectomized mice 1 h after i.m. injection of [1,2-3H]progesterone was determined using liquid scintillation spectrometry. The effects of pre- and post-treatment with large doses of unlabeled steroids on [3H]-progestin accumulation was also determined. The major findings were: (1) Pretreatment with unlabeled progesterone, estradiol benzoate or testosterone propionate, and post-treatment with unlabeled progesterone, failed to reduce [3H]-progestin accumulation and retention in the brain, while these manipulations did reduce, to varying extents, [3H]progestin concentration in the uterus. (2) Across all treatment groups the interpeduncular region of the anterior mesencephalon was found to retain more [3H]progestin radioactivity that all other brain samples. Middle-posterior hypothalamus, mesencephalic reticular formation, medial-dorsal hippocampus, septal, and anterior hypothalamus samples retained higher [3H]progestin concentrations than occipital cortex and plasma samples. [3H]Progestin accumulation in the middle-posterior hypothalamus and mesencephalic reticular formation was also found to be significantly greater than that in the anterior hypothalamus. (3) Chromatographic analyses revealed that approximately 30% of the ethyl acetate extractable radioactivity retained by brain and uterine samples was iso-polar with progesterone, while less than 10% of the radioactivity in the plasma chromatographed as progesterone. The bulk of the remaining radioactivity was divided betwee two more polar peaks, one of which was retained at the origin of the thin-layer plates.

Diencephalic sites responsive to prostaglandin E2 facilitation of sexual receptivity in estrogen-primed ovariectomized rats.

Crystalline prostaglandin E2 (PGE2) induced high levels of sexual receptivity when stereotaxically implanted into the antirior-bala hypothalamic and preoptic regions of estrogen-primed, ovariectomized rats. Anterior- as well as medial basal hypothalamic implants of PGE2 induced a significant elevation of rectal body temperature, but had no effect on open-field activity scores. The possibility that PGE2 exerts its facilitatory effects upon sexual receptivity via an LHRH mechanism is discussed.

Interactions of progesterone and dihydroprogesterone with dihydrotestosterone on estrogen activated sexual receptivity in female mice

Abstract Lordosis behavior in response to a mounting stimulation was quantified in ovariectomized female CD-1 and SW mice primed with estradiol benzoate and either progesterone or dihydroprogesterone. Both progestins were effective in stimulating receptivity, in CD-1 females, while only progesterone was effective in SW females. Dihydrotestosterone given concurrently with both the estrogen and progestin injections was found to have no effect on progesterone stimulated receptivity, but it produced a dose related inhibition of receptivity in the dihydroprogesterone treated females.

Maintenance of sexual behavior in castrate male SW mice using the anti-androgen, cyproterone acetate

The present study was designed to test the hypothesis that cyproterone acetate (C) might selectively block the actions of dihydrotestosterone (D) and via this action, function as an anti-androgen in male sexual behavior. Sexually experienced male SW mice, a strain previously shown to respond to D following castration, were divided randomly into six groups. Beginning on the day after castration, animals received SC injections for 21 days of either testosterone (T), (D), (C), (T+C), (D+C) or vehicle (V). C was found to significantly reduce seminal vesicle and body weights in all androgen treated groups. There was no evidence to support the contention that C selectively blocks the action of D. To the contrary, in sex tests C maintained palpations, thrust mounts, with intromissions and mounts with ejaculations. Indeed, only animals receiving C alone or in combination with T and D exhibited ejaculations throughout the testing. These results suggest that in the SW mouse, C can work like an androgen in the maintenance of male sexual behavior.

Accumulation of 3H-progestins in limbic, diencephalic, and mesencephalic regions of mouse brain

Abstract Ovariectomized and ovariectomized-adrenalectomized Swiss-Webster mice were given ip injections of [ 3 H]-progesterone and sacrificed 60 min later. Analysis of the retained radioactivity suggested that [ 3 H]-progestins were maximally accumulated in the interpeduncular region of the anterior mesencephalon and to a lesser extent in the hypothalamus. The septal area and hippocampus also accumulated more radioactivity than the amygdala, cerebral cortex, cerebellar vermis, olfactory bulb and medulla samples. The pituitary retained more radioactivity than all of the brain samples. There were no consistent differences between adrenalectomized and non-adrenalectomized females.