Richard E. Whalen

Estrogen-progesterone induction of mating in female rats

Abstract Ovariectomized female rats were administered 1, 2, 4, and 8 μg of estradiol benzoate and either 10, 25, 50, 100, or 200 μg of progesterone and were tested for sexual receptivity. The probability of lordosis was related directly to the dose of both steroids. Individual differences in hormone response were marked. Ear wiggling and hopping were primarily related to the dose of progesterone.

Testosterone, androstenedione and dihydrotestosterone: Effects on mating behavior of male rats

Abstract The relative effectiveness of testosterone, androstenedione, and dihydrotestosterone in maintaining mating behavior following castration of male rats was studied. In Experiment 1 testosterone, but not dihydrotestosterone, was found to maintain mating. In Experiment 2 testosterone and androstenedione were found to be equally effective in maintaining mating. Dihydrotestosterone failed to maintain mating and was no more effective than no treatment at all. Testosterone, androstenedione, and dihydrotestosterone significantly enhanced seminal vesicle and penis weight. In Experiment 3 castrated male rats were administered radiolabeled testosterone, androstenedione, or dihydrotestosterone. Radioactivity was found in hypothalamic and seminal vesicle samples indicating that these steroids can be accumulated by brain as well as peripheral androgen-sensitive tissues. It was concluded that the peripherally active steroid dihydrotestosterone probably plays no role in the maintenance of sexual behavior.

Dose-response and time-response relationships between progesterone and the display of patterns of receptive and proceptive behavior in the female rat

Abstract The relationship between administration of progesterone and the display of patterns of receptive (response to the male) and preceptive (female initiated) sexual behavior was examined in ovariectomized, estrogen-primed female rats in a “restrained male” test situation. It was found that the degree of receptivity and proceptivity displayed was directly proportional to progesterone dose and time from progesterone injection (up to 4.5 hr). Higher progesterone doses and longer period of time from progesterone injection (up to 4.5 hr) were both associated with shorter latencies to return to the male following intromission and ejaculation. Receptivity could be induced with estrogen alone but progesterone was required for the display of proceptivity and higher doses of progesterone were needed to effect increases in proceptivity relative to receptivity. Proceptive behavior also occurred in a narrower time range than did receptive behavior. Receptivity alone is characterized as the lowest degree, and receptivity plus proceptivity as the highest degree, of expression of the total behavior pattern of the estrous female rat. Receptivity and proceptivity together constitute a continuum of estrous responsiveness. Increasing the progesterone dose from 0 to 200 μg, and increasing the latency from progesterone injection from 0 to 4.5 hr, were associated with increasing degree of expression of the total behavioral continuum.

Induction of estrus: Estrogen-progesterone interactions

Abstract Accumulating evidence indicates that progesterone can have both facilitatory and inhibitory effects on sexual receptivity and ovulation. The present series of experiments sought to clarify the facilitating and inhibiting actions of estrogen and progesterone on the display of sexual receptivity in the female rat. The first two studies showed that estrogen acting alone can induce receptivity and that 0.5 mg of progesterone facilitates estrogen-induced estrus. The third study sought to demonstrate an inhibitory action of 0.5 mg of progesterone, but failed to do so. Progesterone treatment either before or after the administration of estrogen facilitated and did not inhibit receptivity. Experiment 4 showed that progesterone could inhibit receptivity, but only when administered chronically and at high (5.0 mg) dose levels. A single injection of 10.0 mg of progesterone was found to have no inhibitory action.

Induction of lordosis behavior in female rats by intravenous administration of progestins

Abstract Progesterone is rapidly metabolized by neural cells in the rat. Progesterone could, therefore, act as a “prohormone,” stimulating lordosis behavior in estrogen-primed rats only after metabolic conversion. Were such the case, one might expect one or more of the naturally occurring metabolites of progesterone to be more potent than the parent compound. Estradiol benzoate-primed rats were therefore administered intravenously 200 μg of progesterone or one of five immediate metabolites of progesterone. The steroid 20α-dihydroprogesterone was found to be more potent than progesterone. Both 20α-hydroxy-5α-pregnan-3-one and 3α-hydroxy-5α-pregnan-20-one were less potent than progesterone, but more potent than the vehicle propylene glycol. Neither 5α-pregnane-3α, 20α-diol nor 5α-pregnane-3,20-dione (dihydroprogesterone, DHP) differed from the vehicle in potency. The data suggest that 20α-dihydroprogesterone, which is secreted at high levels during the estrous cycle, could play a role in the regulation of sexual receptivity. The data also suggest that 5α-reduction is probably not crucial for progesterones action.

Differential localization of progesterone uptake in brain, role od sex, estrogen pretreatment and adrenalectomy

Abstract In 3 experiments gonadectomized male and female rats were administered tritiated progesterone. Brain tissues were analyzed for the retention of radioactivity using liquid scintillation techniques. Experiment 1. Estrogen-primed rats were sacrificed 30 min or 60 min after progesterone treatment. There was an increasing gradient of radioactivity from anterior hypothalamus through posterior hypothalamus to the region of the cerebral peduncle in the mesencephalon. Radioactivity levels were higher in females than in males only in anterior hypothalamus and plasma. Experiment 2. Estrogen-primed and non-estrogen-primed rats were sacrified 60 min after progesterone treatment. Estrogen priming had no influence on the retention of radioactivity. The mesencephalic sample retained more radioactivity than the diencephalic tissues. Tissues from females retained more radioactivity than tissues from males. Experiment 3. Adrenalectomized and sham-operated animals were sacrificed 60 min after progesterone treatment. Adrenalectomized animals retained from 27.6 to 51.3% more radioactivity than control animals. Mesencephalic tissues retained more radioactivity than diencephalic tissues. The results suggest the existence of limited capacity binding sites for progesterone in the mesencephalon and diencephalon as well as the pituitary.

Neonatal androgenization and the development of estrogen responsivity in male and female rats

Abstract Male and female rats castrated in adulthood, male rats castrated on the day of birth, and female rats administered 250 μg of testosterone propionate on the day of birth were administered various doses of estradiol benzoate in adulthood and tested for the display of lordosis. The females and neonatally castrated males exhibited a dose-dependent response to estrogen. The control males and neonatally androgenized females showed few lordosis responses when mounted by nonexperimental males regardless of the dose of estrogen administered. The combination of progesterone with the estrogen treatment did not facilitate lordosis responding in the males and neonatally androgenized females, nor did an extensive adaptation period to the test arena, nor did 10 days of treatment with 200 μg estradiol benzoate daily. It was concluded that males and neonatally androgenized females are less responsive to estrogen in adulthood than are females and neonatally castrated males.

The effects of progestins, mineralocorticoids, glucocorticoids, and steroid solubility on the induction of sexual receptivity in rats☆

Abstract In the first experiment, progesterone and its 5α-reduced metabolite, 5α-dihydroprogesterone, dissolved in two different vehicles were compared for their effectiveness in facilitating lordosis behavior in ovariectomized estrogen-primed rats. When dissolved in oil vehicle, 5α-dihydroprogesterone was less effective than progesterone. However, when dissolved in Tween 80 solution, the two progestins were equally effective. In the second experiment, adrenal corticoids dissolved in Tween 80 solution were tested for their relative ability to facilitate sexual receptivity. Progesterone, desoxycorticosterone, and desoxycorticosterone acetate were equally effective in facilitating sexual receptivity. Aldosterone, corticosterone, and corticosterone acetate were no more effective than the vehicle in facilitating sexual receptivity.

P-chlorophenylalanine methyl ester: an aphrodisiac?

P-Chlorophenylalanine methyl ester and the ester plus pargyline have been reported to facilitate sexual mounting behavior in animals, but these studies have shown only a facilitation of homosexual mounting. The present study indicates that these agents do not enhance the probability or frequency of heterosexual interactions in rats.

Anti-estrogen inhibition of androgen induced sexual receptivity in rats.

It has been known for some time that the administration of testosterone propionate or testosterone propionate plus progesterone can induce lordosis behavior in female rats much as can estrogen treatment. It has been suggested that this phenomenon reflects an androgen to estrogen metabolism of the administered testosterone. In the present study it was argued that if this hypothesis were true it should be possible to block androgen induced lordosis with an anti-estrogen which is known to block estrogen induced lordosis. Ovariectomized female rats were administered either testosterone propionate plus progesterone or testosterone propionate plus anti-estrogen plus progesterone. Androgen treatment led to the display of lordosis; anti-estrogen blocked androgen induced lordosis. The anti-estrogen used was CI-628 (CN 55,945-27, Parke, Davis). When this anti-estrogen was administered to male rats it failed to block androgen maintained seminal vesicle weight, or normal male mating patterns suggesting that this agent does not possess anti-androgenic properties. The data are consistent with the hypothesis that androgen induces female lordosis patterns by first being converted to estrogen.