Feminine sexual behavior in rats enhanced by prenatal inhibition of androgen aromatization.
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Biomedical subjects
Publications and source records attributed to L G Clemens.
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In the first experiment ovariectomized female hamsters were administered varying dosages of progesterone (P), dihydrotestosterone (DHT) or CI-628 at the same time (concurrently) as estrogen (EB) or 48 hr after EB (sequentially). All groups also received 500 microgram P 4 hr before being tested for sexual receptivity. P was more effective in reducing receptivity when given sequentially with estrogen than when given concurrently. Thus, the inhibitory effect of P increased with an increased interval between EB and P treatment. More CI-628 than P was required to inhibit lordosis and unlike P, CI-628 was equally effective when given concurrently with EB as when given sequentially. DHT did not inhibit receptivity when given in either paradigm. In the second experiment ovariectomized hamsters were treated with varying dosages of DHT 12 hr before EB. An amount of DHT which had no effect in Experiment 1 significantly inhibited receptivity when given 12 hr before EB. The relative inhibitory effects of these three compounds were discussed in terms of the possible similarities and differences in their mechanisms of action for inhibiting lordosis.
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The prenatal influence of androgen on the development of female sexual behavior in rats was investigated. The nonsteroidal antiandrogen, flutamide (4'-nitro-3'-trifluoromethylisobutyrylanilide; SCH), was administered to pregnant female rats from days 10--22 of gestation in dosages of either 1 mg/mother-day or 5 mg/mother-day. Males and females were gonadectomized in adulthood and tested for the display of lordosis in response to estradiol benzoate (EB) alone or EB with progesterone (P). Males exposed prenatally to either the 1- or 5-mg dosage of flutamide exhibited significantly higher lordosis quotients than controls when given EB alone. The addition of P was without effect in all male groups with regard to estrogen-induced lordosis. Females exposed prenatally to flutamide had significantly higher lordosis quotients than controls when given either 0.175 or 0.25 micrograms EB daily for 3 days. Addition of P to EB treatment significantly facilitated lordosis display in control and flutamide-treated females. The increase of feminine sexual behavior in both males and females of feminine sexual behavior in both males and females resulting from prenatal antiandrogen treatment suggests that androgen, prenatally, inhibits development of female sexual behavior. This androgenic inhibition of sexual receptivity (defeminization) seems to be related to the animal's sensitivity to estrogen in adulthood.
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Male, female and androgenized female rats treated on Days 9, 10 and 11 after birth with either 5-HTP or saline were tested for female sexual behavior in adulthood. It was hypothesized that such pharmacological manipulations of the developing serotonergic system in which Day 12 sex differences have been reported might have an influence on the expression of lordosis behavior. No effect of 5-HTP was found in either normal or androgenized females, even though fluormetric analysis indicated a marked increase in endogenous levels of 5-HT at Day 12. However, males treated with 5-HTP has significantly higher 5-HT levels than 5-HT treated control or androgenized females. In addition, flurometric analysis of norepinephrine, dopamine and serotonin from hypothalamus, mesencephalon and cortex was performed on male and female rats on Day 8, 10, 12 and 14 postnatally to examine the development of various transmitter systems during the early postnatal period.
Intracerebral infusion of prostaglandin E2 (PGE2) facilitated copulatory behaviour of long-term castrated rats. Castrated rats were given daily systemic injections of testosterone propionate (50 microgram) or oil vehicle, and then 30 min before behavioural testing they received an intrahypothalamic infusion of either PGE2 or saline. Rats receiving PGE2 in addition to systemic testosterone showed more copulatory behaviour than those receiving PGE2 or testosterone alone.
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Propylene glycol (glycol) solutions containing either testosterone (T) or estradiol (E2) were infused directly into the preoptic area (POA) of longterm castrated rats in order to reinstate male copulatory behavior. In addition, castrated males were administered T or E2 in the POA in combination with a steroid that has been shown to block the aromatization of testosterone to estradiol, androst-1,4,6-triene-3,17-dione (ATD). The facilitatory action of testosterone on mounting behavior was blocked when it was given in combination with ATD. Animals treated in the POA with glycol +T, glycol +E2 or ATD + E2 all showed significant increases in mounting behavior over preimplant levels. There was no significant rise in the number of intromissions or ejaculations in any of the hypothesis that, at least for mounting behavior, aromatization is necessary for the stimulation of male sexual behavior by testosterone.
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