Either Estradiol Benzoate Research Articles

Role of estrogen receptor α and β in the induction of progesterone receptors in hypothalamic ventromedial neurons

The estrogen induction of progesterone receptors (PRs) in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is critical for the regulation of female sexual behavior. VMNvl neurons express PRs and both types of estrogen receptors (ERα and ERβ), and their sequential activation initiates the molecular mechanisms underlying sexual behavior. To assess the relative importance of each ER subtype in the induction of PRs, we have estimated the total number of PR-immunoreactive neurons and quantified the total amount of PR protein in the VMNvl of adult ovariectomized rats that were injected with either estradiol benzoate (EB) or the specific agonists of the ERα, propyl-pyrazole triol (PPT), and of the ERβ, diaryl-propionitrile (DPN), in different doses and schedules. The administration of EB and of PPT alone, but not of DPN alone, increased the total number of PR-immunoreactive neurons and PR protein levels. When the specific agonists were administered sequentially, the total number of PR-immunoreactive neurons also increased, particularly when PPT was administered before DPN. Conversely, the concomitant administration of PPT and DPN did not increase the number of PR-immunoreactive neurons.The observation that PPT increases the number of PR-immunoreactive neurons and the levels of PR protein far less than EB shows that the estradiol induction of PRs in the VMNvl does not involve solely the activation of the ERα and suggests that it might also implicate the activation of membrane receptors. The present results also show that ERβ activation averts the action of ERα in the induction of PRs.

363 EFFECT OF OESTRADIOL VALERATE OR BENZOATE ON INDUCTION OF A NEW FOLLICULAR WAVE EMERGENCE IN BOS INDICUS COWS AND HEIFERS TREATED WITH NORGESTOMET AURICULAR IMPLANT

Estradiol given during progestin-treatment promotes emergence of a new follicular wave in cattle. The interval from estradiol treatment to follicular wave emergence is dependent on the estradiol preparation, the dose, and possibly the animal category (cows or heifers). Therefore, this experiment aimed to compare the effects of either estradiol benzoate (EB) or estradiol valerate (EV) on the synchrony of ovarian follicular wave emergence in Bos indicus (Nelore) heifers and cows treated with a Norgestomet implant (Crestar�; Intervet, Boxmeer, The Netherlands; factorial 3 � 2 design). Lactating cows (n = 30; 70-90 days postpartum) and cycling heifers (n = 29) were homogeneously assigned, according to the presence of corpora lutea, to six experimental groups (G2EB, G2.5EV, and G5EV for each animal category). At random stages of the estrous cycle (Day 0), the females received an auricular implant and were assigned to receive 2 mg of EB (Farmavet, S�o Paulo, Brazil; 10 cows and 10 heifers; G2EB), 2.5 mg of EV plus 1.5 mg of Norgestomet (10 cows and 10 heifers; G2.5EV; half of a recommended dose), or 5 mg of EV plus 3 mg of Norgestomet (10 cows and 10 heifers; G5EV, full recommended dose) i.m. Transrectal ultrasonography was performed once daily from Day 0 to confirm the follicular dominance (new growing dominant follicle >8 mm in diameter). The day of wave emergence was retrospectively defined as the day when the dominant follicle was first detected at a diameter of 3 mm. Two-way analysis of variance was used to compare the effects of treatments (G2EB, G2.5EV, and G5EV), category (cows and heifers), and the treatments-by-category interaction on the interval from beginning of the treatment to wave emergence. The LSD was used to locate differences among groups and the Bartlett's test revealed heterogeneity of variance. Statistical analysis was conducted by SAS for Windows (SAS Institute, Inc., Cary, NC, USA). There was a significant effect of treatment and category (P < 0.001), but there were no treatments-by-category interactions (P > 0.05). A new follicular wave was induced in all animals after treatment with EB or EV. The heifers given G2EB (2.50 � 0.19a; 2 to 3x days) had a reduced (P < 0.01) and least variable interval (P < 0.05) than those given G2.5EV (4.20 � 0.27b; 3 to 6xy days) or G5EV (6.10 � 0.57c; 3 to 8y days). The cows given G5EV (4.00 � 0.52b; 2 to 6y days) had the longest (P = 0.05) and more variable interval (P < 0.001) than those given G2EB (2.50 � 0.22a; 2 to 4x days), but were similar to those given G2.5EV (3.10 � 0.41ab; 2 to 6xy days). The effect of EB was similar in heifers and cows (P > 0.05); however, the EV or 2.5EV promoted a longer emergence wave interval in the heifers than in the cows (P < 0.05). Analyzing the main effects, cows and heifers given G2EB (2.50 � 0.15a; 2 to 4x days) had a smaller and less variable interval than those given G2.5EV (3.65 � 0.27b; 2 to 6y) or G5EV (5.05 � 0.44c; 2 to 8z). In conclusion, the EV treatment, in both doses (5 or 2.5 mg), resulted in a delayed and more variable interval to emergence of a new follicular wave than 2 mg of EB in Bos indicus cows and heifers treated with a Norgestomet auricular implant. This work was supported by Intervet, Brazil.

Hypothalamic indolamines during embryonic development and effects of steroid exposure

The serotonin system has been implicated in the modulation of endocrine and behavioral components of reproduction. In this study, we examined endogenous hypothalamic indolamines during sexual differentiation and long-term effects of exogenous steroids during this time. In Experiment 1, Japanese quail were studied during the last half of embryonic development and early post-hatch. Samples were taken at embryonic day 10 (E10), E12, E14, E16, hatch (day 0), and days 3 and 5, post-hatch. Hypothalamic indolamines, including serotonin (5-HT) and its metabolite, 5-hydroxy indole acetic acid (5-HIAA) were measured by HPLC-EC detection. Females had relatively higher hypothalamic 5-HT at E14 than males, with both sexes showing increasing levels thereafter. By day 5, post-hatch, hypothalamic 5-HT content was higher in males than in females. When turnover was estimated by comparing relative concentrations of 5-HT to 5-HIAA, males were significantly higher at E12 and E14 than females. These data suggest that there are stage specific changes in the serotonin system, as well as sexually dimorphic patterns in the ontogeny and activity of this system. In Experiment 2, we investigated the effects of embryonic steroid hormone treatment on the serotonin system and on male sexual behavior. Birds were treated with either estradiol benzoate (EB), testosterone propionate (TP) or sesame oil (vehicle control) at selected embryonic days (E10, E12, E14, E16, 0, D3, and D5). At 4 weeks post-hatch, birds were transferred to short photoperiod (16D:8L) for 3 weeks to prevent photostimulated reproductive development. At 7 weeks of age, males were implanted with a 20 mm silastic capsule filled with testosterone and sexual behavior was tested 1 week later. Brains were collected from both males and females, and preoptic area (POA) indolamines were measured. Steroid treatment at E10 or E12 resulted in the loss of male sexual behavior. Moreover, males treated with EB or TP on E12 also had increased POA 5-HT content as adults, compared to control males. Females treated with EB on either E10 or E 12 also had higher POA 5-HT content than control or TP treated females. These data provide evidence for sexual dimorphism in the hypothalamic 5-HT system at specific stages during embryonic development. Moreover, males were sensitive to exogenous EB and TP on E12, whereas females appeared to be affected by EB only and appeared to be sensitive to steroid effects over a longer period of time in development. Moreover, exogenous steroids at E12 in males also correlated with impaired sexual behavioral. These data suggest that long-term effects of embryonic steroid exposure may be mediated in part through effects on the serotonin neurotransmitter system.

Role of estrogen in the acquisition of intravenously self-administered cocaine in female rats

Previous work from this laboratory has revealed that female rats acquired cocaine self-administration at a faster rate than male rats and that a greater percentage of females acquired self-administration [Psychopharmacology 144 (1999) 77.]. It has been suggested that sex differences in stimulant self-administration may be related to ovarian hormones, particularly estrogen. To investigate this possibility, we compared four groups ( n=10) of female rats: ovariectomized (OVX) treated with either estradiol benzoate (EB) or vehicle (VEH), and sham-operated intact (SH) females treated with either the antiestrogen tamoxifen (TAM) or VEH. An autoshaping procedure was used to train rats to lever press for intravenous infusions of cocaine (0.2 mg/kg). The criterion for cocaine acquisition was a mean of 100 self-administered infusions over five consecutive 6-h sessions. Results revealed that 70% of the OVX+EB group and 80% of the SH+VEH group acquired self-administration, while only 30% of the OVX+VEH group and 50% of the SH+TAM group met the acquisition criterion. Rats that had estrogen chemically or surgically blocked exhibited significantly less responding for cocaine over the acquisition testing period, and fewer of these rats met the acquisition criterion compared to intact rats and to OVX rats with estrogen (EB) replacement. The percentages for females with estrogen (70% and 80%) vs. those without (OVX, 30%) were similar to those reported for intact females (70%) and males (30%) in the previous study [Psychopharmacology (2000)]. Taken together, these results suggest that estrogen is a key factor influencing drug-seeking behavior in female rats, and it may underlie sex differences in drug-reinforced responding.

Diurnal Oscillation in Glial Fibrillary Acidic Protein in a Perisuprachiasmatic Area and Its Relationship to the Luteinizing Hormone Surge in the Female Rat

It is well known that the reproductive cycle in the female rat is closely associated with the circadian rhythms of motor activity and that this phenomenon requires the presence of estrogens. Estrogens induce plastic changes in neural connectivity and these changes could be the result of glial modifications. We have measured glial fibrillary acidic protein (GFAP) immunoreactivity in order to localize the area in which the coupling of the circadian rhythms to the generation of the luteinizing hormone (LH) surge may occur. As circadian rhythms are driven by the suprachiasmatic nucleus (SCN), GFAP immunoreactivity was measured in 5 areas of the SCN and surrounding regions. It was measured at two times during daylight (10.00 and 17.00 h) in ovariectomized (OVX) females implanted with Silastic capsules containing either estradiol benzoate (EB) or oil (control). Differences between morning and afternoon GFAP immunoreactivity were observed in a peri-SCN area, dorsal to the SCN and close to the 3rd ventricle, in estrogen-treated as well as in control OVX females. However, this difference increased in the subgroup of EB-treated females which displayed the strongest LH rhythmicity. These results suggest that the peri-SCN area could be an important locus for synaptic changes linking circadian rhythms with the estrogen-induced LH surge.

Organizational effects of estrogens on brain vasotocin and sexual behavior in quail.

Reproductive behavior is sexually differentiated in quail: The male-typical copulatory behavior is never observed in females even after treatment with high doses of testosterone (T). This sex difference in behavioral responsiveness to T is organized during the embryonic period by the exposure of female embryo to estrogens. We showed recently that the sexually dimorphic medial preoptic nucleus (POM), a structure that plays a key role in the activation of male copulatory behavior, is innervated by a dense steroid-sensitive network of vasotocin-immunoreactive (VT-ir) fibers in male quail This innervation is almost completely absent in the female POM and is not induced by a chronic treatment with T, suggesting that this neurochemical difference could be organizational in nature. This idea was tested by injecting fertilized quail eggs of both sexes on day 9 of incubation with either estradiol benzoate (EB) (25 microg, a treatment that suppresses the capacity to show copulatory behavior in adulthood) or the aromatase inhibitor R76713 (10 microg, a treatment that makes adult females behaviorally responsive to T), or with the solvents as a control (C). At 3 weeks posthatch, all subjects were gonadectomized and later implanted with Silastic capsules filled with T. Two weeks later, all birds were perfused and brain sections were processed for VT immunocytochemistry. Despite the similarity of the adult endocrine conditions of the subjects (all were gonadectomized and treated with T Silastic implants providing the same plasma level of steroid to all subjects), major qualitative differences were observed in the density of VT-ir structures in the POM of the different groups. Dense immunoreactive structures (fibers and a few cells) were observed in the POM of C males but not females; EB males had completely lost this immunoreactivity (and lost the capacity to display copulatory behavior); and, conversely, R76713 females displayed a male-typical VT-ir system in the nucleus (and also high levels of copulatory behavior). Similar changes in immunoreactivity were seen in the nucleus of the stria terminalis and in the lateral septum (VT-ir fibers only in this case) but not in the magnocellular vasotocinergic system. These neurochemical changes closely parallel the effects of the embryonic treatments on male copulatory behavior. The vasotocinergic system of the POM can therefore be considered an accurate marker of the sexual differentiation of brain circuits mediating this behavior.

Effect of Long-Term Castration and Long-Term Androgen Treatment on Sexually Dimorphic Estrogen-Inducible Progesterone Receptor mRNA Levels in the Ventromedial Hypothalamus of Whiptail Lizards

In whiptail lizards, as in laboratory rodents, females will respond to exogenous estrogen by increasing progesterone receptor (PR) or PR mRNA in the ventromedial hypothalamus (VMH) while males show an attenuated response to the same treatment. In rodents, neonatal hormone manipulations affect the adult expression of this trait; however, few investigators have examined the effects of hormone treatment in adulthood. Therefore the current study was carried out to determine whether observed sex differences in the estrogen response in adulthood may be modified by steroid hormone manipulation. We castrated male whiptail lizards for 1 week (short term) or 6 weeks (long term). We also gonadectomized female whiptails and implanted them with either a Silastic capsule containing testosterone or an empty capsule. At the end of that time all implants were removed and the animals were injected with either estradiol benzoate (EB) or steroid suspension vehicle and their brains were assayed for PR mRNA expression usingin situhybridization. The results demonstrate that in male whiptail lizards, long-term castration increases sensitivity to estradiol as measured by induction of PR mRNA in the VMH; EB-injected long-term castrated males were not different from EB-injected females. However, long-term androgenization did not attenuate the estrogen response in females. This suggests that attenuation of the estrogen response in males requires activation by testicular secretions, but that females cannot be made to show a male phenotype via testosterone administration.

Peripubertal ontogeny and estrogen stimulation of cholecystokinin and preproenkephalin mRNA in the rat hypothalamus and limbic system

The neuropeptide cholecystokinin (CCK) is expressed in limbic system and hypothalamic nuclei that form a circuit that regulates the display of the female rodent reproductive behavior, lordosis. CCK mRNA and peptide levels fluctuate across the estrous cycle and have been shown to be modulated by estrogen exposure. The objective of these experiments was to examine the expression of CCK mRNA during postnatal development of this limbic-hypothalamic, lordosis regulating circuit, and to determine the age at which CCK mRNA expression becomes responsive to estrogen stimulation, by using quantitative in situ hybridization histochemistry. CCK mRNA levels were below the level of detectability within the circuit during the postnatal period, but increased during the peripubertal period. Rats were injected with either estradiol benzoate (EB), EB and progesterone, progesterone, or oil, and were killed 48 hours later on postnatal day (PND) 15, 20, and 25. Alternate brain sections were processed for CCK and preproenkephalin (PPE) mRNA in situ hybridization histochemistry. EB treatment induced CCK mRNA expression in the central portion of the medial preoptic nucleus and posterodorsal medial amygdala at PND 20 and 25, respectively. However, EB treatment increased PPE mRNA levels within the nuclei of the circuit at all ages examined. Progesterone had neither an independent nor additive effect on the EB induction of these neuropeptide messages. The estrogenic induction of CCK mRNA appears to be dependent on estrogen sensitive pathways of neurotransmission, or components of second messenger pathways which regulate CCK mRNA expression in the adult limbic-hypothalamic lordosis regulating circuit, which are not functional before PND 18-25.

Ovary Mediates the Effects of RU486 Given during Proestrus on the Diestrous Secretion of Luteinizing Hormone in the Rat1

The aim of these experiments was to study the action of proestrous afternoon follicular progesterone secretion on the preovulatory secretion of gonadotropins in the rat. Four-day-cycling rats were given 4 mg of the antiprogestagen RU486 in the morning of proestrus (Day 1), and its effects on the pituitary function during diestrus were compared with those of RU486 given in the morning of estrus (Day 2). The pituitary function was assessed by measuring basal secretion of LH and FSH as well as the pituitary response to either estradiol benzoate (EB) (3 mug/100 g BW at 1300 h on Day 3) or LHRH (100 ng/rat at 1200 h on Day 4). In all experiments, trunk blood was taken at 1300 h on Day 4 to measure serum gonadotropin concentrations. In rats receiving an injection of RU486 on estrus, the absence of only the diestrous progesterone actions increased basal serum concentrations of LH and decreased those of FSH, and as in vehicle-treated controls, EB inhibited and LHRH stimulated LH secretion. In contrast, the absence of both proestrous afternoon and diestrous progesterone actions (as characterized rats treated with RU486 on proestrus) antagonized the inhibitory effect of EB and sensitized the pituitary to LHRH. These effects of RU486 on proestrus are ovary-dependent and eliminated by ovariectomy on metestrus. The increased ovarian secretion of testosterone and estradiol-17 beta during diestrus does not mediate the effects of proestrus-administered RU486 on pituitary function: no differences were found in the serum concentrations of estradiol-17 beta in diestrus between the groups of rats treated with RU486, and administration of the antiandrogen flutamide (2 mg/rat at 0900 h on Days 2 and 3) did not reverse the effects of RU486 on proestrus. In conclusion, the results suggest that in the absence of proestrous afternoon progesterone action, the ovaries of the 4-day-cyclic rat keep the pituitary gland in a state of low sensitivity to the inhibitory effects of estradiol and high sensitivity to the stimulatory effects of LHRH. Moreover, the results suggest that the putative ovarian factors involved are factors other than progesterone, androgens, or estradiol-17 beta.

Effects of Acute Estradiol on 5-Hydroxytryptamine and Dopamine Receptor Subtype mRNA Expression in Female Rat Brain

The aim of the present study was to determine the effect of estradiol-17β, in its positive feedback mode for the release of prolactin and luteinizing hormone (LH), on gene expression of 5-hydroxytryptamine (5-HT) and dopamine receptors. Gene expression was determined by measurement of the levels of receptor mRNA by in situ hybridization in brain sections from adult female rats. The animals were ovariectomized under halothane anesthesia on the morning of diestrus, given a sc injection of either estradiol benzoate (EB) or oil (vehicle), and killed between 1600-1700 h of the next day, presumptive proestrus. The injection of EB in this preparation is known to stimulate a massive surge of LH and prolactin in the late afternoon of presumptive proestrus. The injection of EB produced a significant increase in silver grain densities representing 5-HT 2 receptor mRNA in the dorsal raphe nucleus (DRN) and a significant reduction in these grain densities in the medial septum and diagonal band of Broca. The number of cells expressing 5-HT 2 receptor mRNA was increased by 290% in the DRN and decreased by 25% in the medial preoptic area. Estradiol had no effect on silver grain densities, or numbers or percentages of cells expressing 5-HT 2 receptor mRNA in any of the other nine brain regions or choroid plexus studied, and had no effect on the levels of 5-HT 1A, 5-HT 1C, D 1, or D 2 receptor mRNA in any region studied. These data suggest that the 5-HT 2 receptor is a key receptor involved in mediating the positive feedback stimulation by estradiol-17β of LH and prolactin release. Since estradiol increases 5-HT levels in the DRN, the data raise the intriguing possibility that estrogen positive feedback on LH and prolactin release is mediated by a feed-forward 5-HT drive which results in increased 5-HT release at DRN-derived nerve terminals on hypothalamic neurons which control LH and prolactin release.

Embryonic differentiation of sexual dimorphism in vasotocin and mesotocin levels in chickens

Chicken embryos of both sexes were injected on the tenth day of incubation with either estradiol benzoate (EB), aromatase inhibitor [1,4,6-androstatrien-3, 17-dione (ATD)], antiestrogen [tamoxifen (TAM)], antiandrogen [flutamide (FLU)], or the oil vehicle as control (C). At adulthood, at the age of 26 weeks, 10 chickens of each sex were killed and the amounts of immunoreactive arginine vasotocin (AVT) and mesotocin (MT) in the anterior hypothalamus (AHA), posterior hypothalamus (PHA), neurohypophysis (NHP), and pineal gland (PNL) were determined. Control hens had significantly more AVT in PNL and less MT in AHA and NHP than the corresponding roosters. This sexual dimorphism was affected by the embryonic treatments; TAM increased AVT in AHA of cockerels but not of hens. In both sexes, TAM and FLU increased AVT content in NYP. In males, but not in females, ATD also increased AVT content in the NHP. TAM and FLU administration to the female embryo reduced PNL AVT to the amount present in normal males. None of the treatments effected AHA MT in hens, while in cockerels TAM increased it. In females, TAM and FLU significantly increased NHP MT to the level of C males. In roosters, ATD, TAM, and FLU increased NHP MT further. In hens, but not roosters, FLU reduced MT in PNL. These results indicate that embryonic differentiation of the MT and AVT systems is affected by gonadal steroids in chickens.

Lordosis behavior in intact male rats: Effects of hormonal treatment and/or manipulation of the olfactory system

The aim of this study was to investigate the olfactory mechanisms regulating the display of lordosis behavior in intact Wistar male rats bred in our colony. Gonadally intact males show a low capacity to respond by lordosis to male mounts and were insensitive to manipulations of the olfactory system (exposure to the odor of male urine or accessory bulb removal (AOBR)) which have been previously shown to facilitate the display of lordosis behavior in orchidectomized animals primed with ovarian hormones. Treatment with either estradiol benzoate (EB) or EB and progesterone (P) consecutively did not render these gonadally intact animals sensitive to the effects of AOBR. By contrast exposure to male urine was capable of facilitating the display of lordosis behavior in intact male rats given EB + P consecutively. These results are discussed in the light of previous findings showing that (1) two inhibitory structures, the accessory olfactory bulb and the septal and preoptic areas, are involved in the control of lordosis behavior in the male rat; (2) the effects of olfactory cues on the display of lordosis behavior are dependent on the action of both EB and P in orchidectomized animals.

Luteinizing hormone regulation and sexual behavior in middle-aged female rats.

LH regulation and lordosis were compared in groups of young (3 months old) and middle-aged (8–14 months old) female rats, all of whom were exhibiting regular estrous cycles at the beginning of experimentation. There were four main findings. First, in females having 4-day estrous cycles, the preovulatory surges of LH and progesterone were significantly lower in middle-aged animals. Second, phasic LH release, elicited in ovariectomized females with either estradiol benzoate (EB) and progesterone or EB and mating, was significantly reduced in middle-aged females by 8 months of age. This effect was evident in short and long term ovariectomized females. Third, the postovariectomy rise in LH and the negative feedback response to EB were attenuated in middle-aged females, but not until 11 months of age. Fourth, middle-aged and young females were equivalent in lordotic responses after ovariectomy and EB administration. Plasma steroid measurements at selected time points during the experiments confirmed that the s...

Control of the preovulatory release of luteinizing hormone by steroids in the mouse.

The regulation of the preovulatory release of LH by steroids was examined in the mouse, a species in which ovulation is strongly influenced by priming pheromones. Ovariectomized mice were implanted with estradiol in Silastic capsules to involve negative feedback. Preovulatory-like LH surges then were induced by injections of either estradiol benzoate (EB) or progesterone. LH surges were not observed in the absence of steroid injection. LH surges always occurred at lights out on a 14-h light, 10-h dark cycle on the day after EB injection but occurred on the same day as progesterone injection. The amount of EB or progesterone injected seemed unimportant but, in either case, had to be given within a limited diurnal period of sensitivity. LH surges comparable to those of intact proestrous females were produced either by injecting both EB and progesterone or by manipulating the background dose of encapsulated estradiol. In the latter regard, when ovariectomized females were implanted with a wide range of doses of estradiol (0.1--1000 microgram/capsule), a decided window phenomenon became apparent. That is, LH surging could be induced by steroid injections only within a limited range of background doses of encapsulated estradiol. The relationship of the above findings to the pheromonal control of LH secretion and ovulation in mice is as yet unclear.

Hysterectomy-induced facilitation of lordosis behavior in the rat

The present study investigated the effect of hysterectomy on hormone-induced lordosis behavior. Lordosis quotients (LQ) were measured in hysterectomized-ovariectomized (HO) and ovariectomized-sham hysterectomized (OSH) rats after several treatments including either estradiol benzoate (EB) alone or EB plus progesterone (P) 44 hr later. Testing consisted of placing the females with sexually active males 48 hr after EB. In Experiment 1, HO animals treated with 5 μg/kg EB and 0.5 mg P had significantly higher LQs than OSH animals; groups treated with 10 μg/kg plus P were not different. Experiment 2 showed that a single injection of 50 μg/kg EB resulted in equally high levels of receptivity in both groups. The LQs of HO animals injected with 3 μg/kg for 4 days did not differ from those of OSH animals; however, the administration of 0.5 mg P 24 hr after the fourth EB injection resulted in significantly higher LQs in the HO group (Experiment 3). In Experiment 4, HO rats injected with 5 μg/kg EB and 0.1 mg P 44 hr later displayed higher levels of lordosis behavior than OSH animals. It was concluded that hysterectomy facilitated the lordosis behavior of ovariectomized rats injected with both EB and P and that the mechanism for this potentiation remains to be determined.

Effects of estrogen and prolactin on ovariectomy induced hyperphagia and weight gain in female rats

The hypothesis that prolactin can antagonize the suppressive effects of estrogen on food intake and body weight was tested. In the first experiment, ovariectomized virgin females were injected with either estradiol benzoate (EB), EB and prolactin, or oil. Oil-injected animals gained significantly more weight than did the two EB-injected groups. Oil-treated animals and animals receiving both EB and prolactin ate more than animals injected with EB alone. In the second experiment, ovariectomized and sham-operated animals were injected with either prolactin or saline. Both ovariectomized groups gained weight as did the intact females injected with prolactin. Differences among these groups were not significant. These studies suggest that, while exogenous prolactin has weight enhancing properties in the intact animal, in ovariectomized and estrogen treated animals, prolactin effects are not present.

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.

Neonatal estrogen stimulation and aggressive behavior in female mice

This experiment sought to compare the effects of neonatal androgenization and neonatal estrogenization upon the development of mechanisms for aggressive behavior in mice. Female mice were given either estradiol benzoate (EB) or testosterone propionate (TP) on the day of birth. Other females were given a control injection of oil on the day of birth; male mice received an injection of oil on the day of birth. As adults all mice were gonadectomized, given replacement therapy with TP, and tested in pairs for fighting. Ninety-two per cent of the pairs of females given EB at birth fought following androgen replacement therapy in adulthood. Only 25 per cent of the females given oil at birth fought in adulthood. One hundred per cent of the males and 100 per cent of the females given TP on the day of birth fought in adulthood. It was concluded that administration of estrogen to neonatal female mice facilitates the differentiation of androgen sensitive mechanisms for adult aggressive behavior. In this regard, neonatal estrogenization appears to mimic the effects of neonatal androgenization.