Central implants of dilute estradiol enhance the satiety effect of CCK-8.

The following studies evaluated whether direct placement of estradiol into different brain areas could increase the satiating potency of CCK in female rats. In Experiment 1, estradiol implants in the PVN, but not in the VMN or third ventricle, significantly enhanced the satiety actions of CCK (5.0 micrograms/kg). In Experiment 2, a lower dose of CCK (0.5 micrograms/kg) suppressed food intake in females with estradiol implants in the PVN but not in animals with implants in the VMN or preoptic area. In both experiments, estradiol implants in the PVN significantly lowered food intake and body weight during the 2-day period of hormone treatment. Implants in other areas had no significant effects on feeding or body weight. These data support the hypothesis that the satiety effect of CCK is enhanced by estradiol and suggest that the PVN is involved in the interaction between CCK and estradiol.

Antagonism of estrogenic effects on feeding behavior by central implants of anisomycin.

The following experiment determined whether the estrogenic suppression of food intake is dependent upon changes in protein synthesis within neurons of the paraventricular nucleus of the hypothalamus (PVN). Ovariectomized rats were treated centrally with anisomycin-filled or empty (control) cannulae in the PVN. Females were injected with either 2.0 micrograms of estradiol benzoate (EB) or the oil vehicle and the inner cannulae were removed 2 h later. EB injections significantly lowered food and water intake in the central control group but not in animals given PVN implants of anisomycin. Body weight gain decreased for all females. EB induced comparable levels of female sexual behavior in both groups, demonstrating that anisomycin implants did not affect the ability of estradiol to stimulate lordosis. These findings indicate that the effects of estradiol on food intake require the activation of protein synthesis in estrogen-sensitive PVN neurons.

Modulation of the satiety effect of cholecystokinin by estradiol.

Data obtained from a wide variety of mammalian species indicate that feeding behavior can be influenced by changes in endogenous estrogens and by exogenous estrogenic treatments. The present experiment represents an initial investigation of the hypothesis that the suppression of food intake by estradiol is mediated by an enhancement of the satiety effect of cholecystokinin (CCK). Twenty-four female rats were ovariectomized and implanted either with a 5% estradiol silastic capsule or an empty capsule on the day of surgery. Three weeks later, animals received IP injections of CCK-octapeptide (5.0 or 10.0 micrograms/kg) or saline after 24-h food deprivation. Food and water intake were measured 60 min after treatment. Although CCK suppressed feeding in all subjects, the effects on food intake were greater in estradiol-treated females. CCK injections also reduced water intake, but there was no interaction between estradiol and CCK on drinking. These findings indicate that the inhibitory effect of CCK on food intake is enhanced in females treated with a physiological dose of estradiol, and suggest that the effects of estradiol on feeding behavior may be mediated by a potentiation of the satiety effect of CCK.

Effects of PVN lesions on the responsiveness of female rats to estradiol.

Previous research has shown that the paraventricular nucleus of the hypothalamus (PVN) is an important site of action for the effects of estradiol on feeding behavior. The recent finding that estrogenic stimulation of the PVN lowers food intake without inducing lordosis suggests that the effects of estradiol on feeding and sexual behaviors are organized separately within the brain. Whether the effects of estradiol on food intake can be attenuated by PVN lesions is therefore a question of practical and theoretical interest. In this experiment we examined the behavioral responsiveness of females with PVN lesions to peripheral treatment with estradiol. 32 adult, female rats received either bilateral or sham lesions of the PVN. All subjects were ovariectomized 2 weeks after the lesion. 2 Weeks following ovariectomy, half of the animals were injected with 2 micrograms of estradiol benzoate (EB) for 3 days, and half were injected with the oil vehicle. 10 days later, the treatment conditions for each subject (oil or EB) were reversed. Histological analysis indicated that 9 females had bilateral lesions of the PVN and 4 had bilateral lesions of the dorsomedial nucleus of the hypothalamus (DMN); 11 animals received sham lesions. Compared with oil treatment, EB injections significantly lowered water intake and body weight gain in all groups. However, food intake was suppressed in the DMN and sham but not in PVN-lesioned females. In addition, statistical analyses indicated that EB treatment induced similar levels of female sexual behavior in all groups. Thus, PVN lesions did not interfere with the ability of estradiol to stimulate lordosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in ingestive behaviors and body weight following intracranial application of 17 alpha-estradiol.

The present experiment was conducted to determine if central implants of 17 alpha-estradiol could influence food intake, water intake, and body weight in ovariectomized rats. A total of fifteen animals were fitted with bilateral guide cannulae in the paraventricular nucleus (PVN) and stimulated unilaterally with cholesterol and 17 alpha-estradiol in each side of the brain. Compared with cholesterol treatment, 17 alpha-estradiol implants in the PVN significantly lowered food intake and body weight but did not affect water intake. These findings indicate that the PVN is a brain region responsive to the effects of 17 alpha-estradiol on feeding behavior, and support the hypothesis that the effects of estrogens on ingestive and reproductive behaviors are organized separately within the brain.

Effects of intracranial implants of dihydrotestosterone on the reproductive physiology and behavior of male guinea pigs.

An experiment was conducted to determine whether the intracranial application of dihydrotestosterone (DHT), a nonaromatizable androgen, would stimulate male guinea pig mating. Of three castrate groups studied, one was a control group in which subjects were implanted both in the medial preoptic area (MPOA) and under the skin with cannulae containing cholesterol (NoDHT). Males in one of the experimental groups received implants of cholesterol in the MPOA plus subcutaneous implants containing DHT (ScDHT). Members of the other experimental group were subcutaneously implanted with cholesterol and simultaneously given intracranial implants of DHT (IcDHT). Compared to either the NoDHT control group of the ScDHT experimental group, greater numbers of males in the IcDHT group displayed mounts (P less than 0.01), intromissions (P less than 0.01), and ejaculations (P less than 0.001). Additionally, the hypothalamic implants of DHT had no significant effects on peripheral target tissues. These data indicate that androgenic stimulation of the guinea pig brain is sufficient to activate masculine sexual behavior in this species.

Central implants of diluted estradiol: independent effects on ingestive and reproductive behaviors of ovariectomized rats.

The present experiment was undertaken to evaluate the hypothesis that the effects of estrogens on feeding and sexual behaviors are organized separately within the brain. Thirty-three ovariectomized rats were implanted with bilateral guide cannulae aimed at either the paraventricular nucleus (PVN), medial preoptic area (MPOA), or posterior hypothalamus (PH). Subjects that received PVN implants were stimulated with either undiluted estradiol, a 3:1, or 10:1 mixture of cholesterol and estradiol. Animals in the other groups were treated with undiluted estradiol. All females were stimulated unilaterally with cholesterol and estradiol, yielding a total of 66 stimulation sites. Histological analysis revealed that, compared to cholesterol implants, undiluted estradiol in the PVN reduced food intake and body weight. More importantly, diluted estradiol implants in the PVN significantly lowered food intake and body weight. In contrast, undiluted estradiol in the MPOA, PH, or ventromedial hypothalamus (VMH) had no significant effects on feeding or body weight. Analyses of variance revealed significant main effects of implant location on female sexual behavior. Newman-Keuls tests indicated that diluted estradiol implants in the PVN produced lordosis quotients and quality scores that were significantly lower than those obtained with VMH implants. The possibility that the behavioral changes observed were due to peripheral rather than central effects of the hormone was evaluated by comparing the results of implants that produced vaginal cell cornification to those that did not. There were no significant differences between these groups on any of the other dependent variables, indicating that peripheral estradiol sufficient to induce vaginal cell cornification was neither necessary nor sufficient to account for the behavioral changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of sexual behavior in male rats by combined subcutaneous and intracranial treatments of 5 alpha-dihydrotestosterone.

When given peripherally, 5 alpha-dihydrotestosterone, the major androgenic metabolite of testosterone, is relatively less effective than testosterone in activating sexual behavior of castrated male rats. In order to test the possible central nervous system effects of dihydrotestosterone more directly, we castrated Long-Evans rats, gave them a behaviorally subthreshold dose of dihydrotestosterone placed subcutaneously in Silastic capsules (ScDHT), and then additionally treated the rats with intracranial implants of crystalline dihydrotestosterone (IcDHT, N = 12), testosterone (IcT, N = 12), or cholesterol (IcCHOL, N = 10) placed in the medial preoptic area. The peripheral ScDHT treatment maintained sexual organ weights of castrated males at levels comparable to those of intact males, but did not in itself significantly activate mating behavior. The addition of IcT or IcDHT to this treatment regimen significantly increased the number of males displaying mounting behavior, intromissions, and ejaculatory behavior (P less than 0.05) compared to males with IcCHOL implants. There were no significant differences between the group given IcT and the group given IcDHT. Results of this study support the hypothesis that the nonaromatizable androgen 5 alpha-dihydrotestosterone can act in the rat brain to influence male sexual behavior. In addition, these data lead us to suggest that the relative ineffectiveness of dihydrotestosterone versus testosterone when given systemically may reflect differences in bioavailability of these hormones to the brain following such treatment.

Body temperature and temperature gradients: changes during the estrous cycle and in response to ovarian steroids.

Rectal temperature, body weight, and vaginal membrane condition were monitored in female guinea pigs in order to determine the pattern and magnitude of changes in these variables across the estrous cycle and as a result of treatment with ovarian hormones. A thermistor probe was used to measure rectal temperatures at depths of 4 and 8 cm and to determine the temperature gradient between these two sites. Data collected across the estrous cycles of 18 intact females were aligned by day of vaginal membrane rupture, the estimated time of ovulation. Compared to measurements during the midluteal phase of the estrous cycle, rectal temperatures increased significantly one to three days prior to vaginal membrane rupture. In addition, a significant periovular decline was observed in the temperature gradient and in body weight. Treatment of ovariectomized females with 3 micrograms estradiol benzoate for 3 days (EB) followed by a single injection of 0.4 mg progesterone on the 4th day (P) led to biphasic changes in temperature. Compared to a control group which received injections of 0.2 ml corn oil vehicle for 4 consecutive days (OIL), EB significantly increased rectal temperature measured at the depth of 4 cm, but had no significant effect on measurements taken at a depth of 8 cm. The temperature difference between these two sites also decreased significantly. Rectal temperatures at both 4 cm and 8 cm sites dropped significantly following injection of progesterone. Ovarian hormones therefore have significant effects on body temperature of guinea pigs, effects which, in combination with other evidence, lead us to suggest that some of the observed temperature variations may be related to estrogen-induced changes in peripheral vasodilation or other mechanisms of heat loss.

Behavioral consequences of hormonal deprivation on the responsiveness of female rats to estradiol.

Female rats which had been ovariectomized either 7 days earlier (short-term deprivation, N = 11) or 35 days earlier (long-term deprivation, N = 11) were tested for their response to treatments of estradiol benzoate (6.0 micrograms/kg body weight) and progesterone (1.2 mg/kg). The long-term deprived females showed less sexual behavior than females deprived for only 7 days prior to treatment. In particular, lordosis quotients after treatment with estradiol alone were significantly lower in the long-term deprived females, t(20) = 3.194, p less than 0.01. Following a supplemental progesterone injection, the lordosis scores and the number of proceptive behaviors displayed by long-term deprived females were also significantly lower than these measures in short-term deprived females, t(20) = 3.481, p less than 0.01 and t(20) = 3.737, p less than 0.01, respectively. In contrast, the two groups did not differ in the degree to which estradiol treatment suppressed food intake, F(1,20) = 2.306, N.S. Likewise, the changes in water intake and body weight produced by estradiol treatment did not differ significantly between the two groups, F(1,20) = 0.118, N.S. and F(1,20) = 0.452, N.S., respectively. The results obtained from the sex behavior tests are generally consistent with the notion that hormonal deprivation alters the responsivity or sensitivity of female rats to estradiol. However, these changes do not appear to involve a general decline in receptor sensitivity or number, because the ability of estradiol to suppress ingestive behaviors was not diminished in the long-term deprived females.

Duration of hormonal deprivation: influences on physiological and behavioral responsiveness to estradiol.

A total of 54 ovariectomized female guinea pigs were divided into three groups and tested six times at 2-week intervals for their responsiveness to exogenous ovarian hormones (3 days of 4 micrograms/kg estradiol benzoate plus 1 day of 0.4 mg/kg progesterone) or control injections (0.2 ml oil vehicle). Two weeks after ovariectomy, treatment with estradiol significantly reduced food intake and body weight, and also produced vaginal membrane rupture in 98.1% of the females. When tested for sexual behavior at 4, 6, and 8 hr after the progesterone injection, 29 of the subjects (53.7%) displayed lordosis in response to manual stimulation. Twelve weeks after ovariectomy, the effects of estradiol on food intake, body weight, and vaginal membrane condition had not diminished. However, the overall proportion of females from which lordosis could be elicited declined to 27.8%. Biweekly injections of estradiol benzoate plus progesterone to one of the groups of females did not prevent this decline in the sexual response. Based on these results, it was concluded that the observed reduction in behavioral lordosis does not represent a general decline in the responsiveness of ovariectomized guinea pigs to estrogenic stimulation, but may involve changes in their responsiveness to progesterone or in other mechanisms more specifically associated with sexual behavior.

Maintenance of target tissue and sexual behavior with dihydrotestosterone in male rats and guinea pigs.

The ability of dihydrotestosterone (DHT) to maintain androgen-sensitive target tissue and masculine sexual behavior was examined in castrated male rats and guinea pigs. Silastic capsules filled with DHT amd implanted subdermally at the time of castration were found to stimulate epididymal tissue in a dose-dependent manner in both species. However, differences were found in the behavioral effectiveness of this steroid. Capsules containing sufficient DHT to maintain peripheral structures were effective in maintaining copulatory behavior of castrated guinea pigs, but not of the similarly treated rats.

Intracranial estradiol in ovariectomized guinea pigs: effects on ingestive behaviors and body weight.

The present study was undertaken to evaluate the effects of intracranial estradiol stimulation on food intake (FI), water intake (WI), and body weight (BWt) of ovariectomized guinea pigs (GPs). Thirty-five GPs were implanted with bilateral guide cannulae aimed at either the ventromedial hypothalamus, paraventricular nucleus (PVN), or preoptic area and then were stimulated unilaterally with cholesterol and estradiol 17-beta, yielding a total of 70 stimulation sites. Across all GPs, estradiol implants significantly reduced FI, WI and BWt relative to implants of cholesterol. The possibility that the behavioral changes observed were due to the peripheral rather than central effects of the implants was evaluated by comparing the results of stimulations which produced vaginal membrane rupture (VMR) to the results of cases without VMR. There were no significant differences between these groups on any of the dependent variables studied, indicating that peripheral estradiol sufficient to induce VMR was neither necessary nor sufficient to account for the behavioral changes. Histological analysis revealed that implants in the ventromedial-arcuate region (VM/ARC) and PVN significantly lowered FI and BWt, with the effects being greatest in the PVN. Placements in other areas, on the average, did not significantly suppress FI or BWt. The effect of central estradiol on WI was more diffuse. No significant effect of implant location was found for the estrogenic suppression of drinking. These findings are the first demonstration that estradiol applied to particular brain areas can lower FI, WI, and BWt of ovariectomized GPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of female hormonal condition on body weight of male partners: dependence on testicular factors.

Four experiments explored the short-term effects of female estrous condition or gonadal hormones on male body weight. Body weights of male guinea pigs and their ovulating female partners were initially found to show a significant periovular suppression relative to those of female cagemates that were not ovulating at that time. Similar effects in male rats have been hypothesized to result from postcopulatory increases in circulating testosterone and the conversion of that testosterone to estradiol. For evaluation of the probable role of the guinea pig testes in the observed phenomenon, intact and castrated male guinea pigs were housed with ovariectomized females. Female estrus, induced by injecting the females with estradiol and progesterone, resulted in an immediate decline in body weight of the intact male partners, but the body weight of castrated male partners was unaffected. Additional tests evaluated the direct effects of estradiol and testosterone on body weight of male guinea pigs. Injections of up to 1 mg per day of testosterone propionate were insufficient to produce short-term suppression of body weight in either intact or castrated males. However, treatment of the males with estradiol readily reduced their body weight. Overall, these results are not consistent with the hypothesis that short-term reductions in body weight of mated males result from immediate postcopulatory increases in circulating testosterone. It is suggested that other, possibly more estrogenic, testicular factors may play a role in the observed phenomenon.

Independent effects of estradiol on water and food intake.

Six experiments examined the effects of estradiol on ingestive behaviors of guinea pigs. Estradiol treatment was found to reduce water intake independently of its actions on food intake and body weight. In the first experiment, minimum intake and body weight of intact female guinea pigs coincided with rupture of the vaginal membrane, the estimated time of ovulation. In a second experiment, injections of 3 micrograms of estradiol benzoate per day to ovariectomized females significantly depressed food intake, water intake, and body weight, compared with oil injections. The ratio of water intake per gram of food intake did not change significantly during the estrous cycle or following estradiol injections, results suggesting that the reduced drinking might be a consequence of the reduced feeding. However, reducing food rations to 30% below ad lib levels in Experiment 3 by itself had no significant effect on drinking. In Experiment 4, therefore, ovariectomized females were first placed on a food ration 30% below ad lib levels and then injected daily with either 3 micrograms of estradiol benzoate or oil. Compared with oil injections, these estradiol injections significantly reduced water intake, while food intake did not decline significantly. In these experiments, the reduction in food intake was therefore neither a sufficient nor a necessary condition for the estradiol-induced suppression of water intake. The last two experiments verified that estradiol has independent actions on feeding. The daily water ration was reduced to 30% below ad lib levels in Experiment 5, with no significant effect on food intake. In the sixth experiment, the water ration was first reduced to 30% below ad lib levels, and then the ovariectomized females were injected with either oil or 3 micrograms of estradiol benzoate per day. With this reduced water ration, the estradiol significantly suppressed food intake while producing only minimal and insignificant changes in water intake. These findings established that estradiol can independently influence water intake and food intake in the guinea pig and thereby indicate that estradiol operates through di different mechanisms to produce these two effects.