Acute, nongenomic vasodilatory action of estradiol is attenuated by chronic estradiol treatment

Deficiency of estradiol or chronic estrogen treatment may alter the responses to this hormone in many tissues. A possible interaction between the acute nongenomic and the chronic effects of estradiol on microvessels have not been investigated yet. In the present study we have investigated whether acute in vitro vasodilatory action of estradiol on a small artery is altered by chronic estradiol pretreatment. Female rats were surgically ovariectomized and subjected to either estradiol replacement therapy (estradiol propionate, 450 micrograms/kg/week) or vehicle administration for 5 weeks. Cylindrical segments of the saphenous artery were studied using videocomputerized microarteriography in vitro. Estradiol, in concentrations of 10(-6) to 10(-4) M relaxed norepinephrine precontracted vessel segments in a dose-dependent manner. Magnitude of relaxation observed in arteries of estradiol replaced animals was significantly smaller at all concentrations than that of nonreplaced ovariectomized rats; maximal relaxation in the control ovariectomized group was 64.5% +/- 3.6%, while it was 34.3% +/- 4.2% only in the ovariectomized and estradiol replaced group (P < 0.001). Comparison of acute relaxations in response to papaverine and nifedipine failed to prove a reduced activity of the general relaxation machinery in estradiol replaced animals. We conclude that chronic estradiol replacement can downregulate the acute nongenomic vasorelaxation effect of this hormone in small arteries of ovariectomized rats.     

A prenatal source for defeminization of female rats is the maternal ovary

Sexual behavior in laboratory rats is influenced by a variety of factors in the perinatal environment. Male rats are masculinized and defeminized in response to circulating testosterone perinatally. Females undergo a process of feminization but in some cases are exposed to testosterone. Previous work has shown that during prenatal development female rats normally undergo a partial masculinization and defeminization of sexual behavior as reflected by altered responsiveness to gonadal hormones in adulthood. In the present study we investigated whether the maternal ovary influences adult females' responsiveness to gonadal hormones. Pregnant rats were ovariectomized on Day 10 of pregnancy and their offspring tested for sexual behavior in adulthood. Following ovariectomy pregnancies were maintained by administration of systemic progesterone. In addition the ovariectomized pregnant rats were given one of three daily treatments (Days 10-21): 0.2 microgram estradiol benzoate in sesame oil and 0.1 cc propylene glycol, 5 mg of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) in 0.1 cc propylene glycol, or 0.1 cc propylene glycol. A control group was generated from SHAM operated mothers given daily control injections of propylene glycol and sesame oil. Offspring were ovariectomized in adulthood and tested for display of feminine sexual behavior in response to estradiol benzoate and progesterone or estradiol benzoate alone. Masculine sexual behavior was measured in response to testosterone propionate (TP). Feminine sexual behavior was enhanced in offspring from ovariectomized mothers given only progesterone replacement during pregnancy. Offspring from mothers treated with ATD displayed the greatest elevations in feminine sexual behavior. Estradiol treatments of ovariectomized mothers prevented the increase in feminine potential seen in offspring in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved model for the induction of proestrus-like gonadotropin surges in long-term ovariectomized rats

In long-term (greater than 4 wk) ovariectomized rats the positive response of the gonadotropin release apparatus to a priming dose of estradiol is moderate as compared with that of proestrous rats exposed to endogenous estradiol. In the present study, high sensitivity to estrogen was restored in long-term ovariectomized rats by pretreatment with estradiol benzoate (EB, 20 micrograms, day 0) and progesterone (P, 2.5 mg, day 3). Estradiol benzoate (20 micrograms) given on day 5 induced proestrus-like surges of LH and FSH in the afternoon on day 6. Additional administration of P (2.5 mg at noon on day 6) had a facilitatory effect. Stimulation of LH release could be evoked in rats by the described regimen 1, 6 or 50 wk after ovariectomy. The long-term ovariectomized rat injected with EB and P as described might provide a useful model for neuroendocrinological investigations on the gonadotropin surge mechanism.     

Critical progesterone requirement for maintenance of pregnancy in ovariectomized rats

The minimum progesterone concentration required to maintain the pregnancy was studied by varying doses of progesterone given subcutaneously to rats ovariectomized on Day 8 of pregnancy. Injecting 3 mg progesterone plus 200 ng oestradiol benzoate daily provided serum progesterone values between 25.4 +/- 7.0 and 35.2 +/- 6.2 ng/ml throughout Days 10-19 which were significantly lower than normal levels (P less than 0.05), but resulted in 93.6% of fetal survival on Day 19 which was not significantly different from 93.3% in the control group. Injecting 2 mg progesterone plus 200 ng oestradiol benzoate daily gave progesterone values between 13.2 +/- 4.6 and 19.0 +/- 6.2 ng/ml and could not maintain fetal viability to Day 19 (14.2%, P less than 0.05 compared with control group). Critical times to supplement progesterone in rats ovariectomized on Day 8 or Day 15 were studied by varying the time of progesterone implantation after ovariectomy. Progesterone implants were administered 8, 12 and 24 h after ovariectomy on Day 8 and 24, 36 and 48 h after ovariectomy on Day 15. On Day 8, progesterone replacement could be delayed to 8 h but not 12 h, while on Day 15, progesterone replacement could be delayed up to 36 h but not 48 h after ovariectomy without affecting fetal survival.     

Ovariectomy upregulates expression of estrogen receptors,NOS, and HSPs in porcine platelets

Platelets participate in normal and pathological thrombotic processes. Hormone replacement in postmenopausal women is associated with increase risk for thrombosis. However, little is known regarding how platelets are affected by hormonal status. Nitric oxide (NO) modulates platelet functions and is modulated by hormones. Therefore, the present study was designed to determine how loss of ovarian hormones changes expression of estrogen receptors and regulatory proteins for NO synthase (NOS) in platelets. Estrogen receptors (ER alpha and ER beta), NOS, heat shock proteins 70 and 90 (HSP70 and HSP90), caveolin-1, -2, and -3, calmodulin, NOS activity, and cGMP were analyzed in a lysate of platelets from gonadally intact and ovariectomized female pigs. Expression of ER beta and ER alpha receptors, endothelial NOS (eNOS), HSP70, and HSP90 increased with ovariectomy. NOS activity and cGMP also increased; calmodulin was unchanged. Caveolins were not detected. These results suggest that ovarian hormones influence expression of estrogen receptors and eNOS in platelets. Changes in estrogen receptors and NOS could affect platelet aggregation in response to hormone replacement.     

The role of estradiol 17β in the activation of the uterus during premature labor and the effect of naproxen,an inhibitor of prostaglandin synthesis

Fifty-two pregnant rats were ovariectomized on day 16 of gestation to induce estrogen and progesterone deficiencies and the animals were divided into four Groups. Ovariectomy alone (Group A) resulted in the premature delivery of 21% of the fetuses. When ovariectomy was followed by estrogen treatment restoring normal estrogen levels (Group B), premature delivery of the fetuses increased to 96%. Daily injections of 25mg/kg b.w. Naproxen (Group C), given from the day of ovariectomy to reduce prostaglandin synthesis, completely prevented premature delivery if the animals received no estradiol treatment and reduced prematurity to 50% if estradiol had been administered (Group D).It is concluded that the estrogen and progesterone deficiency, induced by ovariectomy, provokes a regulatory imbalance which promotes premature delivery. This imbalance is enhanced when the estradiol levels are restored to normal values, probably because estradiol increases the synthesis of prostaglandin, the intrinsic myometrial stimulant. Naproxen, an inhibitor of prostaglandin synthesis, restores the regulatory balance, partially or completely, depending on the estrogen levels.     

Pituitary progestin-metabolizing enzyme activities in the aged female rat.

Progesterone 5 alpha-reductase activity and 5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) enzymic activities (NADH-linked and NADPH-linked) were measured in anterior pituitaries (AP) from aged female rats during three stages of reproductive senescence (constant estrus: CE; repeated pseudopregnancies: PSP; and anestrus: AN). To assess ovarian influence on these enzymes during these stages of reproductive aging, we also determined enzyme levels from ovariectomized rats from each stage treated with estrogen or vehicle. Progesterone 5 alpha-reductase and NADH-linked 3 alpha-HSOR activities were 2-fold higher in pituitaries of CE rats as compared to those of PSP and AN rats. NADPH-linked 3 alpha-HSOR levels did not differ among the three stages. All three enzyme levels were elevated 2- to 5-fold as compared to the corresponding enzyme levels from young cycling rats. After ovariectomy (10 days), 5 alpha-reductase activity in PSP and AN rats was elevated 3- to 4-fold relative to mean levels in intact PSP and AN rats. Ovariectomy had no effect on 5 alpha-reductase levels in CE rats. Under similar conditions, young cycling rats exhibit a 10-12-fold increase. Treatment of ovariectomized PSP and AN rats for 3 days with estradiol benzoate (10 micrograms/day) restored 5 alpha-reductase levels. Ovariectomy had no effect on the NADPH-linked 3 alpha-HSOR levels in CE, PSP or AN animals which is similar to that observed with young rats. Ovariectomy also had no effect on the NADH-linked 3 alpha-HSOR levels except for the CE group. The ovariectomized CE rats exhibited reduced pituitary NADH-linked 3 alpha-HSOR levels (30%). In contrast, young rats exhibit elevated pituitary NADH-linked 3 alpha-HSOR levels after ovariectomy (4- to 5-fold). These changes suggest the possibility that altered processing of progesterone and its 5 alpha- and 3 alpha-reduced products may be one means by which the effectiveness of progesterone is reduced during aging. The results also suggest an altered ovarian role in the regulation of these enzymes.     

Chronic treatment with estrogen receptor agonists restores acquisition of a spatial learning task in young ovariectomized rats

Previous work has shown that continuous estradiol replacement in young ovariectomized rats enhances acquisition of a delayed matching-to-position (DMP) T-maze task over that of ovariectomized controls. The mechanism by which estradiol confers this benefit has not been fully elucidated. This study examined the role of selective estrogen receptor agonists of ERα, ERβ, and GPR30 in the enhancement of spatial learning on a DMP task by comparing continuous estradiol replacement with continuous administration of PPT (an agonist of ERα), DPN (an agonist of ERβ), or G-1 (an agonist of GPR30) relative to gonadally intact and ovariectomized vehicle-treated controls. It was found that ovariectomy impaired acquisition on this task, whereas all ER selective agonists restored the rate of acquisition to that of gonadally intact controls. These data suggest that estradiol can work through any of several estrogen receptors to enhance the rate of acquisition on this task.     

Effect of ovariectomy and estrogen supplementation on brain acetylcholinesterase activity and passive-avoidance learning in rats

The effect of ovariectomy and estrogen treatment on the brain acetylcholinesterase activity and cognition in rats was investigated in this study. Ovariectomized and nonovariectomized rats were treated subcutaneously with estradiol dipropionate for 8 d. In the single-trial, passive-avoidance test all the groups showed significant learning and retention of memory as evident by the increase in transfer latency time in trial 2 as compared with trial 1. No-transfer response was significantly increased in the estradiol-dipropionate-treated ovariectomized (80%) and nonovariectomized (60%) group as compared with the ovariectomized (30%) group. Specific activity of acetylcholinesterase was assayed spectrophotometrically in salt-soluble and detergent-soluble fractions of various brain areas: frontal cortex, cerebral cortex, striatum, hippocampus and hypothalamus, thalamus, pons, medulla, and cerebellum. The effect of ovariectomy and estradiol dipropionate was varied in both fractions of these brain areas. Estradiol dipropionate treatment could restore the acetylcholinesterase activity to the control level only in the detergent-soluble fraction of hypothalamus and salt-soluble fraction of hypothalamus, thalamus, and medulla in ovariectomized rats. The results indicate that ovariectomy alters acetylcholinesterase activity in the brain areas but not in a uniform manner and affects only qualitative aspects of cognitive function, which could be improved by estrogen supplementation.     

Structural and histomorphometric evaluations of ferutinin effects on the uterus of ovariectomized rats during osteoporosis treatment

AimsThe effects of chronic administration of Ferutinin (phytoestrogen found in the plants of genus Ferula), compared with those elicited by estradiol benzoate, were evaluated, following ovariectomy, on the uterus of ovariectomized rats as regard weight, size, structure and histomorphometry.Main methodsThe experimental study included 40 female Sprague–Dawley rats, assigned to two different protocols, i.e. preventive and recovering. In the preventive protocol, ferutinin (2 mg/kg/day) was orally administered for 30 days, starting from the day after ovariectomy; in the recovering protocol, ferutinin was administered, at the same dosage, for 30 days starting from the 60th day after ovariectomy, when osteoporosis was clearly established. Its effects were compared with those of estradiol benzoate (1.5 μg per rat twice a week, subcutaneously injected) vs. vehicle-treated ovariectomized controls and vehicle-treated sham-operated controls. Uteri were removed, weighed and analysed under both the structural and histomorphometrical points of view.Key findingsOur data show that ferutinin acts, similarly to estradiol benzoate, on the uterus stimulating endometrial and myometrial hypertrophy; this notwithstanding, the phytoestrogen ferutinin, in contrast to estrogen treatment, appears to increase apoptosis in uterine luminal and glandular epithelia.SignificanceFerutinin, used in osteoporosis treatment primarily for bone mass recovering, seems in line with an eventual protective function against uterine carcinoma, unlike estrogens so far employed in hormone replacement therapy (HRT).     

Action of the sexual hormones on the endogenous norepinephrine of the central nervous system (author's transl)]

The effects of ovariectomy and the injection of sexual hormones on the norepinephrine (NE) content in different areas of the central nervous system were studied in the Wistar female rat. The ovariectomy increased the NE in the hypothalamus, cerebellum and the medulla oblongata. The estradiol benzoate did not modify the NE levels in the ovariectomized rats. Progesterone decreased the NE in the hypothalamus and testosterone dipropionate increased it in the brain hemispheres. It seems possible that the hypersecretion of FSH would increase the synthesis of NE in castrated animals through the potentation of the tyroxine-hydroxylase activity. Increase in testosterone synthesis was probably responsible for the raise in NE levels. The progesterone moderated the effects of the ovariectomy, probably through feed-back mechanisms involving the hypothalamic-hypophyseal tract.     

The influence of estradiol and progesterone and melatonin supplementation on TNF-alpha levels in ovariectomized and pinealectomized rats

The aim of this study was to investigate the effect of estradiol and progesterone and melatonin supplementation on TNF-alpha levels in ovariectomized and pinealectomized rats. The study was carried out on 42 adult, Spraque-Dawley strain female rats aged 6 months and weighing 200-250 grams. The rats were divided into 6 groups, each group contained 7 rats. Group 1: Sham-ovariectomized (Sham-Ovx), Group 2: Ovariectomized (Ovx), Group 3: Ovx and estradiol (E) and progesterone (P) supplemented (Ovx+E-P) group, Group 4: Ovx+E-P+Melatonin (M) supplemented group, Group 5: Ovx Pinealectomized (Pnx) group, Group 6: Ovx - Pnx+E-P supplemented group. Serum TNF-alpha levels were determined after 4 weeks application period. Group 6 (Ovx-Pnx+E-P) has the highest serum TNF-alpha compared with other groups while group 2 (ovariectomized), has the lowest levels (P<0.001). Group 5 was higher than groups 1, 2, 3 and 4 (P <0.001). The results of the study show that ovariectomy reduces the serum level of TNF-alpha, but estradiol and progesterone application prevents this reduction in ovariectomized rats. However, pinealectomy intensifies the increases in TNF-alpha levels in ovariectomized and estradiol and progesterone supplemented rats, whereas melatonin reduces TNF-alpha levels in ovariectomized rats.     

The modes of the anterior hypothalamic area as the regulatory center for the gonadotropin release

The effects of the anterior hypothalamic area (AHA) implants of gonadal steroid estrogen and progesterone as well as the effects of electrical stimulation and electrolytic lesion confined in this area on the gonadotropin secretion were investigated in ovariectomized estradiol (20 microgram sc)-primed adult Wistar rats housed in light and temperature controlled room. Progesterone implants evoked the rise of serum LH by 6 hr whereas estradiol implants suppressed serum FSH by 24 hr after implantation. Electrical stimulation effectively depleted both gonadotropins with a latency not shorter than 6 hr. The lesion significantly prevented FSH elevation investigated at 72 hr post ovariectomy and potentiated FSH secretion in response to estradiol treatment at 3 week post ovariectomy. The result revealed the involvment of the AHA in LH release mechanism which required progesterone activation while its involvement in FSH regulatory mechanism depended upon estrogen. The area was elucidated as the inhibitory as well as the stimulatory loci for the feedback action of estrogen on FSH release.     

Estrogen supplement prevents the calcium hypersensitivity of cardiac myofilaments in ovariectomized rats

Our previous biochemical and mechanical studies have demonstrated an increase in Ca2+ sensitivity of cardiac myofilaments in ovariectomized rats. To test whether the body weight gain associated with ovariectomy contributed some effects to the changes in myofibrillar functions, the relations of pCa (-log Ca2+ molar concentration) to actomyosin adenosine triphosphatase (ATPase) activity of isolated myofibrillar preparations from 10-week pair-fed ovariectomized rats were compared with those from sham-operated controls. Despite similar body weights, the maximum myofibrillar ATPase activity was significantly lower in pair-fed ovariectomized rats as compared to that of sham-operated controls. In addition, the pCa-actomyosin ATPase relationship of pair-fed ovariectomized hearts still demonstrated a significant leftward shift in pCa50 (-log half-maximally Ca2+ activation) from that of sham-operated controls. To find out which hormone was responsible for the observed increase in myofibrillar Ca2+ sensitivity, different sex hormone supplemental regimens were administered to ovariectomized rats. Subcutaneous injection of estrogen (5 microg/rat) or estrogen plus progesterone (1 mg/rat) three times a week could effectively prevent the changes in body weight, heart weight, and uterine weight of the ovariectomized animals. Moreover, supplements of either estrogen or progesterone could prevent a decrease in maximum ATPase activity. In contrast, only the estrogen replacement could abolish the Ca2+ hypersensitivity of the myofilaments in these ovariectomized rats. These results suggest differential cardio-regulatory effects of ovarian sex hormones on the Ca2+ activation of the myofilaments.     

The effect of estrogen treatment on scopolamine inhibition of lordosis.

Previous evidence indicates that the cholinergic muscarinic antagonist, scopolamine, inhibits lordosis in female rats. In the experiments reported here, the effects of various doses and repeated administrations of estrogen on the scopolamine inhibition of lordosis were examined. In the first experiment, intraperitoneal injections of scopolamine (1 mg/rat) completely inhibited lordosis in ovariectomized rats primed with low doses of estradiol benzoate (0.25 or 0.5 micrograms for 3 days) and progesterone (500 micrograms). However, scopolamine was significantly less effective in inhibiting lordosis in females primed with a higher dose of estradiol benzoate (25 micrograms for 3 days) and progesterone (500 micrograms). When hormone priming was repeated on subsequent weeks, scopolamine continued to inhibit lordosis in females that received 0.25 micrograms estradiol benzoate but was less effective in females primed with 0.5 micrograms. Scopolamine failed to inhibit lordosis in females treated with 25 micrograms estradiol benzoate on these later tests. In the second experiment, various doses of scopolamine (1, 2, or 4 mg/rat) were administered intraperitoneally to females primed with the highest dose of estradiol benzoate (25 micrograms) and progesterone (500 micrograms). Lordosis was inhibited equally by all scopolamine doses during the first week. As in the first experiment, scopolamine failed to inhibit lordosis at all doses on subsequent weeks of testing. These results indicate that the ability of scopolamine to inhibit lordosis is reduced by increasing the dose or the number of estrogen exposures. Because higher doses of scopolamine failed to restore its inhibitory effect on lordosis an upregulation of muscarinic receptors by estrogen cannot account for the reduced effectiveness of scopolamine.     

Estrogenic effects of zearalenone on the expression of progestin receptors and sexual behavior in female rats

Zearalenone is a resorcylic acid lactone compound that is produced by fungal infection of edible grains and is believed to influence reproduction by binding to estrogen receptors. In order to study the potential estrogenic effects of this compound in the brain, we examined the effects of zearalenone on the expression of neuronal progestin receptors and feminine sexual behavior in female rats. Ovariectomized rats were treated with zearalenone (0.2, 1.0, or 2.0 mg), estradiol benzoate, or vehicle daily for 3 days. They were then either perfused, and progestin receptors visualized by immunocytochemistry, or injected with progesterone and tested for sexual receptivity with male rats. Progestin receptor-containing cells were counted in the medial preoptic area and ventromedial hypothalamus. The two highest doses of zearalenone increased the concentration of neuronal progestin receptors, as did 10 microg of estradiol. The highest dose of zearalenone (2 mg) also induced progestin receptor staining density comparable to that of 10 microg of estradiol benzoate. In behavioral tests, ovariectomized animals treated with 2 mg of zearalenone followed by progesterone showed levels of sexual receptivity comparable to females treated daily with estradiol benzoate (2 microg) followed by progesterone. These studies suggest that, although structurally distinct and less potent than estradiol, zearalenone can act as an estrogen agonist in the rat brain.     

Possible role of mitochondrial dysfunction in central neurodegeneration of ovariectomized rats

In the present study, ovariectomized Sprague-Dawley rats were used to mimic the pathological changes of post-menopausal females with genistein and estradiol benzoate (EB) as substitutes for endogenous estradiol. Measurements of hippocampal ATP content, mitochondrial ATP content and the rate of mitochondrial ATP synthesis in the hippocampus indicated that after ovariectomy, brain energy metabolism of the rats presented a transient change in hippocampal ATP content which was significant from the 6th to the 8th day after ovariectomy. The change on the 6th day was the most noteworthy. Mitochondrial ATP content and the rate of mitochondrial ATP synthesis of the hippocampus were also lowered. However, after using EB or genistein, the three indicators returned to normal. It is suggested that mitochondrial dysfunction may play a key role in Alzheimer's disease (AD) of the post-menopausal female, and may serve as the target for endogenous estrogen and exogenous phytoestrogen. In addition, genistein, which possesses the properties of estrogen but not its side effects such as carcinogenicity, could reverse the bioenergetic defects of ovariectomized rats and perhaps be used as a substitute for estradiol to prevent or treat central neurodegeneration in post-menopausal women.     

Divergent regulation of gonadotropin subunit mRNA levels by androgens in the female rat.

To examine the effects of gonadal steroids on the pretranslational regulation of the gonadotropin subunits in the female, adult female rats, beginning 7 or 28 days after ovariectomy, received daily injections of testosterone propionate (T), dihydrotestosterone propionate (D), or estradiol benzoate (E) for 7 days. Intact cycling females and ovariectomized rats that received vehicle served as controls. Serum was obtained for LH and FSH levels to assess changes in gonadotropin secretion. Total RNA from individual rats was recovered and analyzed by blot hybridization with specific radiolabeled cDNA probes for the alpha, LH beta, and FSH beta subunits. Autoradiographic bands were quantitated and standardized to mRNA levels in the intact animals. Ovariectomy resulted in a rise in serum gonadotropin levels and all three gonadotropin subunit mRNA levels. Estrogen replacement resulted in suppression of alpha, LH beta, and FSH beta mRNAs whether given at 7 or 28 days after ovariectomy. In contrast, whereas androgen replacement decreased alpha and LH beta mRNAs, D or T did not consistently suppress FSH beta mRNAs. We conclude that chronic estrogen administration to the castrated female rat uniformly suppresses all three gonadotropin subunit mRNA levels. In female rats, as in male rats, chronic androgen administration fails to negatively regulate FSH beta mRNAs.     

Opioidergic control of luteinizing hormone release in the female rabbit: influence of ovariectomy and steroid replacement on pulsatile secretion

The influence of ovariectomy and steroid replacement on naloxone-induced changes in pulsatile secretion of luteinizing hormone (LH) in the female rabbit was examined. Blood samples were taken every 5 min through an indwelling catheter in the rabbit ear artery, and plasma was stored until assayed for LH by established radioimmunoassay procedures. In the intact animal, saline injection had no effect on LH secretion. Although naloxone (10 mg/kg) caused a 7-fold increase in mean LH pulse amplitude by 30 min after injection, this increase was not statistically significant because 5 of 11 animals did not respond. In animals ovariectomized 48 h previously, naloxone significantly increased LH concentration by 194% at 23 min after injection. When long-term ovariectomized rabbits were treated with estradiol benzoate and then were given naloxone, no significant increase in LH was observed, although many animals did respond. Treatment of long-term ovariectomized rabbits with 1 microgram estradiol benzoate and 100 micrograms progesterone or 1 mg testosterone propionate on Days 1 and 3 and naloxone on Day 4 resulted in a significant increase in LH 19-24 min later. Although there was an increase in pulse amplitude, no change was detected in pulse frequency after naloxone. These data suggest that the hypothesis of steroid-opioid coupling in the control of LH secretion is not applicable to the female rabbit.     

Progesterone reduces the effect of the serotonin 1B/1D receptor antagonist, GR 127935, on lordosis behavior

Ovariectomized rats were hormonally primed with 10 μg estradiol benzoate or with estradiol benzoate plus 500 μg progesterone. Rats received a bilateral infusion with 200 ng of the 5-HT_1B/1D receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-1-1′-biphenyl-4-carboxamide hydrochloride (GR 127935), into the ventromedial nucleus of the hypothalamus (VMN), followed by a 5 min restraint or home cage experience. In estrogen-primed females that had experienced minimal handling between ovariectomy and use in the experiment, infusion with the water vehicle transiently inhibited lordosis behavior, and the 5-HT_1B/1D receptor antagonist amplified this inhibition. There were no effects in rats hormonally primed with estrogen and progesterone. Handling for two days before the experiment reduced the effects of the infusions in estrogen-primed rats. However, when a 5 min restraint experience followed infusion with GR 127935, there was a significant decline in lordosis behavior that persisted for 10 to 15 min after the experience. Regardless of the prior experience or type of infusion, the addition of progesterone to the hormonal priming completely prevented the lordosis inhibition. These findings are consistent with prior evidence that progesterone protects against the inhibitory effects of a 5 min restraint experience on lordosis behavior. Moreover, these are the first experiments to demonstrate an inhibitory effect of a selective 5-HT_1B/1D receptor antagonist in the VMN on lordosis behavior of estrogen primed, but not estrogen and progesterone primed, ovariectomized rats.