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Biomedical subjects

G N Wade

Publications and source records attributed to G N Wade.

At least 127 records · Page 7Linked to original sources

Ovarian hormones and meal patterns in rats: effects of progesterone and role of gastrointestinal transit.

Three experiments determined: (1) whether progesterone treatment would reverse the effects of estradiol benzoate (EB) on meal patterns of ovariectomized (OVX) rats, and (2) whether changes in gastrointestinal transit were responsible for the EB-induced changes in meal patterns. Progesterone (5 mg/day) reversed the effects of EB by increasing meal size and decreasing meal frequency in OVX, EB-treated rats. Progesterone had no effect on these measures in OVX rats that were not given EB. In a comparison of the rate of gastrointestinal transit, the rate of gastrointestinal transit was found to be faster in OVX rats injected with EB daily for two weeks than in OVX, oil-treated controls as measured under anesthesia with infusion of ten ml of liquid diet. However, this alteration in gastrointestinal transit does not appear to be responsible for the decreased meal size of EB-treated, OVX-rats, because the gastrointestinal changes are not observed 34-38 hr after an EB injection, a time at which meal size is already affected.

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Sequential inhibition of sexual behavior by progesterone in female rats: comparison with a synthetic antiestrogen.

When a large dose of progesterone was administered to ovariectomized rats 24 hr after a 2-microgram injection of estradiol benzoate (EB), sexual receptivity was inhibited at 54 hr (sequential inhibition). Larger doses of progesterone (1 mg) were required to inhibit the induction of sexual receptivity when tested at 54 hr than were necessary to facilitate at 30 hr. This inhibition was not due to copulatory stimuli from the first test, because inhibition occurred even when the first test was omitted. The inhibition was dose dependent on estradiol; increasing the EB priming dose offset the inhibition caused by 1 mg of progesterone. The results of an experiment that dissociated behaviorally the antiestrogenic action of progesterone from that of a synthetic antiestrogen, CI-628, are consistent with the notion that progesterone and synthetic antiestrogens inhibit the neural effects of estradiol by separate mechanisms of action.

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Concurrent inhibition of sexual behavior, but not brain [3H]estradiol uptake, by progesterone in female rats.

Chronic injections of high doses of progesterone (5 mg) and low doses of estradiol benzoate (EB; 2 microgram) resulted in less sexual behavior than did low doses of progesterone (.5 mg) and low doses of EB. In a typical procedure for inducing sexual behavior, EB and progesterone were given sequentially, separated by 42 hr. High levels of progesterone (2.5 and 5 mg) administered concurrently with EB inhibited the induction of sexual receptivity. Increasing the dose of EB from 2 microgram to 6 microgram or 10 microgram offset this inhibition. High doses of progesterone (5 mg) administered simultaneously or 2-16 hr prior to EB inhibited the induction of sexual behavior, but the inhibition waned when progesterone was administered 48 hr prior to EB. A single injection of progesterone (1 mg) that did not inhibit the induction of sexual behavior when administered concurrently with EB did inhibit lordosis when distributed into five injections (.2 mg) every 4 hr. The results of two experiments in which progesterone did not inhibit the uptake or retention of [3H]estradiol by brain cell nuclei suggest that the antiestrogenic action of progesterone in the central nervous system is not to interfere with the binding of estradiol.

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Effects of ovariectomy and estradiol on body weight and food intake in gold thioglucose-treated mice.

Two experiments investigated the effects of ovariectomy and estradiol replacement on the body weight and food intake of mice that had previously been treated with either gold thioglucose or saline. Ovariectomy and estradiol benzoate injections altered food intake in gold thioglucose-treated mice as much as in saline controls. Ovariectomy increased body weight in saline controls but it was without effect on the body weight of gold thioglucose-treated mice.

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Sex differences in sensitivity of food intake, body weight, and running-wheel activity to ovarian steroids in rats.

The effects of sex and experimental androgenization on the responsiveness of food intake and running-wheel activity to exogenously administered ovarian hormones were investigated in adult, gonadectomized rats. Food intake was found to be analogous to lordotic behavior in that males and neonatally androgenized females were relatively insensitive to the influences of either estradiol benzoate (EB) or progesterone (P). Running-wheel activity, however, could be differentiated from food intake in that males responded the same as females to the effects of EB and P. Androgenized females (500-mug testosterone propionate on the third day of life) showed a response to EB quantitatively equivalent to that of nonandrogenized females, but they had a longer latency to respond. The estrogen-antagonistic effects of P were confirmed for both of these behaviors, and there was a positive correlation between the magnitude of the responses to EB and P.

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Androgenic control of food intake and body weight in male rats.

Castration of adult male rats produces a delayed (by approximately 1 mo), permanent hypophagia and reduction in weight gain. This contrasts with the rapid, transient hyperphagia and increased weight gain caused by ovariectomy in female rats. Injections of testosterone propionate (TP) stimulate food intake and weight gain in castrated males. Neither 5alpha-reduction nor aromatization of the testosterone molecule plays an important role in the stimulation of these measures by TP. The 5alpha-reduced metabolite of TP, 5alpha-dihydrotestosterone propionate (DHTP), is less effective in increasing eating and weight gain than is TP. Very high doses of TP may actually reduce weight gain with prolonged treatment (2-6 wk). It is likely that this reduced weight gain is due to aromatization of TP to an estrogen. The nonaromatizable androgen, DHTP, does not reduce weight gain even in very high doses, and concurrent progesterone injections reverse the weight-reducing actions of high TP doses.

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Some effects of ovarian hormones on food intake and body weight in female rats.

Ovarian steroids affect the food intake and body weight of rats. These effects are probably mediated by estradiol and progesterone, since these 2 hormones are more effective than their principal metabolites (estrone and 5alpha-pregnane-3,20-dione, respectively) in altering the food intake and body weight of ovariectomized rats. Estradiol seems to affect food intake by lowering the set point about which body weight is regulated in a dose-dependent fashion. These actions of estradiol can be attenuated or completely blocked by concurrent injections of progesterone. Estradiol-treated ovariectomized rats are far more responsive to the weight- and appetite-promoting actions of progesterone than are ovariectomized-adrenalectomized rats, suggesting that the principal action of progesterone on energy balance may be to interfere with the effects of estradiol.

Adrenal Glands↗

Role of estrogens in androgen-induced spontaneous activity in male rats.

Three experiments tested the hypothesis that testosterone may be aromatized to an estrogen to stimulate running-wheel activity in rats. Aromatizable (testosterone propionate: TP) and nonaromatizable (dihydrotestosterone propionate; DHTP) androgens were compared with estradiol benzoate (EB) for the ability to induce running in castrated male rats. The DHTP had no effect on running. The TP increased running, but EB was more than 100 times as effective. A relatively small dose of a specific estrogen antagonist, MER-25, was shown to attenuate the effects of both EB and TP on male running. The MER-25 did not affect the running of castrated, oil-treated male rats and did not inhibit the running induced by food deprivation.

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