Estradiol Capsules Research Articles

Vasoactive intestinal peptide levels in the hypothalamus and anterior pituitary do not change in association with the pre-ovulatory prolactin surge in the rat

We examined whether vasoactive intestinal peptide (VIP) is involved in the preovulatory prolactin (PRL) surge in the rat. Ovariectomized adult rats implanted sc with an estradiol capsule 2 days previously were decapitated at hourly intervals between 1100–1800 h. The plasma PRL and luteinizing hormone showed an evident surge at 1700 h and 1800 h, respectively. The anterior pituitary PRL content was significantly lower at and after 1600 h than at 1100 h. However, there was no significant change in the VIP content in the suprachiasmatic nucleus, paraventricular nucleus, median eminence or anterior pituitary throughout the entire period of observation. Since all of these regions are known to be involved in the VIP synthesis and/or release, the present results appear to cast some doubt on previous studies reporting a significant role for VIP in the generation of the pre-ovulatory PRL surge.

The Timing of Neuroendocrine Sexual Maturity in the Male Lamb by Photoperiod1

In spring-born female lambs, the long days of summer, followed by their gradual decrease, provide the seasonal cue necessary to time puberty to early autumn (approximately 30 wk of age). Male lambs begin spermatogenesis during mid-summer, some 20 wk before puberty occurs in females. Unlike young female lambs, male lambs attain puberty at the same age under a variety of photoperiodic manipulations, raising the possibility that sexual maturation in males is not affected by photoperiod. We have reinvestigated the role of photoperiod on puberty in the male lamb, using a more precise indicator of reproductive activation--the decreased sensitivity of the hypothalamo-pituitary axis to inhibitory steroid feedback leading to increased LH secretion. To test whether photoperiod can influence the onset of neuroendocrine sexual maturation in male lambs, this study compared the timing of the decrease in sensitivity to inhibitory steroid feedback in two groups of males under opposite photoperiodic conditions. Eight males were reared indoors from 2 wk of age under conditions simulating the natural increasing and decreasing day lengths around the summer solstice; an additional 7 males were exposed to a reversed simulated natural photoperiod in which the changes in day length were amplified and accelerated relative to outdoor conditions. Both groups of lambs were castrated and received s.c. implants of Silastic estradiol capsules to provide a constant steroid feedback signal. The timing of reduction in sensitivity to estradiol negative feedback, measured as a sustained increase in circulating of LH above 1.0 ng/ml, was used to define neuroendocrine sexual maturity.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of the Luteinizing Hormone Surge by Chlordimeform in Ovariectomized, Steroid-Primed Female Rats

The midcycle surge of luteinizing hormone (LH) from the pituitary provides the physiological trigger in the mammalian female for the process of ovulation. Accordingly, any agent that compromises the LH surge could function as a reproductive toxicant. Since ovariectomized (OVX) rats implanted with oestradiol capsules will exhibit daily afternoon surges, such animals can serve as a useful model for the investigation of toxicant-induced alterations in this functional hormonal event. The acaricide chlordimeform (CDF) has previously been found to decrease serum LH, probably by altering the hypothalamic noradrenergic transmitter control of LH secretion. Consequently, the present study focused on the effect of acute CDF administration on the appearance of the induced LH surge. Single intraperitoneal injections of CDF (0, 10, 25, 50 mg/kg) in OVX, oestradiol-implanted female Long-Evans rats approximately 5 hr prior to the expected surge caused a complete suppression at 25 and 50 mg/kg. Ten mg/kg had no effect on surge amplitude, but advanced the LH peak by 2 hr. The observed suppression did not persist beyond the day of CDF administration. Earlier dosing at 11 or 18 hr prior to the surge was without effect. Since CDF has been found to elevate serum corticosterone (CORT), 10 mg CORT/rat were given at different times prior to the surge. Twenty hr after administration only a partial lowering was seen; 5 hr exposure were ineffective. This indicates that an indirect adrenal effect was not the principal route, but may accompany an action of CDF on the hypothalamic mechanisms regulating the surge and becomes evident after more prolonged exposure.

The action mechanism of the pineal gland in inhibiting sexual receptivity of female rats: (I). Is it concerned with the extrahypothalamic inhibitory pathway?

Monosodium L-glutamate (MSG), as a neurotoxin, was administered subcutaneously at a dose of 4 mg/g body weight to rat pups on days 1 and 3 postnatally. The sexual receptivity expressed as lordosis quotient (LQ) in MSG-treated female rats (2.5 months old) was significantly lower than that of the normal female ones, and this poor sexual receptivity of MSG-treated females could be improved by pinealectomy at the age of six weeks. In order to investigate the relationship between the inhibitory role of the pineal gland and the extrahypothalamic inhibitory pathway, normal control and MSG-treated rats were ovariectomized and implanted subcutaneously with estradiol capsule (20% estradiol benzoate, in 2mm silastic tube) at the age of 2.5 months. Three days after implantation, sexual receptivity was observed. Then, the anterior roof deafferentation (ARD) was preformed one week later and the sexual receptivity in both groups was compared again. The results showed that there was no significant difference of the lordosis response between the MSG-treated and the control groups before ARD, and the level of restoration by ARD in LQ of MSG-treated rats was similar to that of the control group. It seems that the extrahypothalamic inhibitory pathway of sexual receptivity may not be influenced by neonatal MSG-treatment. Our previous results indicated that the behavioral sensitivity to estradiol was altered by ARD. However, in the present study, the lordosis responses of MSG-treated and pinealectomized female rats were not significantly different from that of the control group after ovariectomy and exogenous estradiol implantation. This means that the behavioral sensitivities to estradiol were not changed by MSG-treatment or pinealectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol-induced prolactinomas: differential effects on dopamine in posterior pituitary and median eminence

Prolactin release is inhibited by dopamine and stimulated by estradiol. Dopamine is released from nerve terminals in the median eminence and posterior pituitary. Estradiol may act directly on the anterior pituitary or by modulating the two dopaminergic systems. Estradiol treatment induces the formation of prolactinomas in Fischer 334 rats. Therefore, this strain was chosen as the experimental model. The first objective was to determine whether estradiol differentially regulates the two dopaminergic systems. The second objective was to explore whether the anterior pituitary in estradiol-treated rats acquires the capability for de novo synthesis of dopamine. Rats were ovariectomized and implanted with estradiol capsules (OVEX + E2). Controls were untreated ovariectomized rats (OVEX). Three weeks thereafter, rats were killed. Anterior and posterior pituitaries and medial basal hypothalami (MBH) were removed and individually incubated for 60 min in Hank's balanced salt solution containing 10 μCi [ 3H]-tyrosine. The median eminence was then dissected from the MBH. Tissues were homogenized in perchloric acid and the supernatant fluids were extracted with alumina. Both endogenous and tritiated dopamine were simultaneously quantitated by HPLC. Prolactinoma formation in OVEX + E2 rats was confirmed by dramatic rise (50-fold) in plasma prolactin levels and marked enlargement (3-fold) of the anterior pituitary. Estradiol treatment caused a significant 60% reduction in both dopamine content and synthesis in the median eminence. In contrast, estradiol treatment affected neither dopamine content nor synthesis in the posterior pituitary. There was no evidence for de novo synthesis of dopamine in anterior pituitaries from either OVEX or OVEX + E2 rats. We conclude that the two dopaminergic systems which regulate prolactin secretion, exhibit a differential response to estradiol.

Acute suppression of FSH secretion by oestradiol in the ovariectomized rhesus monkey

Using long-term ovariectomized rhesus monkeys, we examined the ability of oestradiol to decrease circulating FSH concentrations in the absence of other ovarian factors. Daily blood samples were obtained from untreated monkeys for 8 days, followed by insertion of oestradiol capsules after the Day-8 sample was taken. Samples were then taken on Days 9-15, the capsules were removed after the Day-15 sample, and samples were obtained on Days 16-19. Serum was assayed for concentration of oestradiol, FSH and LH by RIA. The concentration of FSH (ng/ml) in serum did not change during the first 8 days before oestradiol treatment (overall mean = 356 +/- 55) but decreased from the Day-8 value of 320 +/- 8 to 190 +/- 42 on Day 9 and by Day 15, after 7 days of oestradiol treatment, had reached a nadir of 20 +/- 5. By Day 17, i.e. 2 days after removal of the oestradiol capsules, serum FSH had increased (P less than 0.05) to 92 +/- 23 with a further increase (P less than 0.05) on Day 19 (171 +/- 16). This study demonstrates that, unlike in rats, mice, and sheep, administration of oestradiol alone to ovariectomized rhesus monkeys reduces immunoreactive serum FSH to concentrations measured in intact animals.

Pulsatile LH Secretion during Sexual Maturation in the Female Sheep: Photoperiodic Regulation in the Presence and Absence of Ovarian Steroid Feedback as Determined in the Same Individual

This study in the female lamb determined if photoperiod influences pulsatile LH secretion before puberty. Moreover, we reevaluated the hypothesis that the photoperiod-modulated decrease in responsiveness to ovarian steroid inhibition which results in increased pulsatile LH secretion during sexual maturation reflects an increase in direct central nervous system 'drive' of gonadotropin secretion. The experimental approach was to monitor pulsatile LH secretion in the presence and absence of estradiol negative feedback during development in the same individuals. This was accomplished by the periodic replacement and removal of constant-release estradiol capsules every 3 weeks in ovariectomized lambs (OVX) which were raised in photoperiods that delay or permit normal puberty. A new algorithm was used for identification of episodes of LH secretion. In OVX lambs in the permissive sequence of photoperiods (long days of 16L:8D until 18 weeks of age, followed by short days of 8L:16D), LH pulse frequency was low in the presence of estradiol early in life at 9 weeks of age, but increased at later ages. LH pulse frequency in the presence of estradiol feedback was not associated with that in the absence of estradiol replacement. LH pulse frequency was high throughout development in the absence of estradiol and increased further at the time when responsiveness to estradiol negative feedback decreased. In lambs raised in the inhibitory sequence of photoperiods (short days until 18 weeks of age followed by long days), LH pulse frequency in the presence of estradiol remained low throughout the duration of the experiment, but in the absence of estradiol, LH pulse frequency increased with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Relative roles of oestradiol and of the uterus in the maintenance of the corpus luteum in the pseudopregnant brown hare (Lepus europaeus).

Brown hares were made pseudopregnant by sterile matings or PMSG-hCG treatment (day of mating or hCG injection = Day 0 of pseudopregnancy). Progesterone secretion by the CL began 3-4 days after the ovulatory stimuli, reached maximum on Days 8 to 11 and decreased thereafter to reach low levels from Day 9 to 18, depending on the female. Cauterization of all large ovarian follicles on Day 7 resulted in an immediate luteolysis in young females, but had no effect in older ones. Oestradiol capsules implanted from Day 7 to Day 46 were able to maintain progesterone secretion until at least Day 30, in intact females as well as in females with all large follicles cauterized. Hysterectomy on Day 7 or 8 was followed by an immediate drop in progesterone concentrations; oestradiol capsules implanted at the time of hysterectomy prevented the drop in progesterone values, which remained elevated until Day 38. The induction of ovulation in females hysterectomized 2 months before resulted in CL of slightly shortened life-span. The injection of PGF-2 alpha on Day 7 of pseudopregnancy was followed by an immediate luteolysis. These results suggest that oestradiol secreted by the large ovarian follicles is the main luteotrophic factor in the brown hare. In old hares, the large amount of interstitial tissue could secrete oestrogens, and thus maintain pseudopregnancy. On Day 7 of pseudopregnancy, the uterus secretes a luteotrophic substance acting either directly on the ovary, or via the pituitary, to maintain oestradiol secretion by the follicles. In long-term hysterectomized females, the CL would be able to develop independently of any trophic substance, but for a reduced duration.

Estrogen Interconversions in the Induced Cycle in Female Rhesus Monkeys1

To determine the extractions and interconversions of estrone and estradiol across and within the uterus, [3H]estradiol and [14C]estrone were infused at a constant rate in six ovariectomized female rhesus (Macaca mulatta) monkeys. Studies were done on Days 9, 14, and 23 of artificial menstrual cycles induced by the timed insertion and removal of Silastic capsules of estradiol and progesterone. Measurements of estrogen radioactivity were made from peripheral arterial blood and uterine venous blood as well as from endometrial biopsy samples. A significant increase occurred in the conversion of estradiol to estrone measured within the uterus on Day 23 compared to Days 9 and 14. The conversion of estrone to estradiol, measured within the uterus, fell progressively from Day 9 to Day 23, but this decrease was not significant. The extractions and interconversions across the uterus, and the overall interconversions of estrone and estradiol were not significantly different on Days 9, 14, or 23 of the cycle. Thus, we have been able to confirm in vivo the increase in the activity of the 17 beta-hydroxysteroid dehydrogenase, the enzyme responsible for estradiol to estrone interconversions, shown earlier by studies done in vitro. However, the increase in 17 beta-hydroxysteroid activity in the uterus is not reflected in the overall interconversions of estrone and estradiol as reflected by measurements in peripheral arterial blood.

Age-Related Changes in the Diurnal Rhythm of Serotonin Turnover in Microdissected Brain Areas of Estradiol-Treated Ovariectomized Rats*

The purpose of this study was to determine whether 1) a diurnal rhythm in serotonin turnover is present in specific hypothalamic nuclei of middle-aged ovariectomized rats and 2) in middle-aged animals exposure to estrogen can induce the pattern of serotonin dynamics which appears necessary for the occurrence of an LH surge in young rats. Young (3-4 month old) and middle-aged (8-10 month old) rats which demonstrated estrous cyclicity were bilaterally ovariectomized. Seven days later half of the young and middle-aged animals received Silastic estradiol capsules. On day 9 post ovariectomy the groups were again divided; half of the rats in each group were killed at 0800, 1200, 1800, and 2400 h. Remaining animals were treated with pargyline (75 mg/kg BW, ip) at these times and were killed 10 min later, and the following brain areas were microdissected and analyzed for serotonin (5HT) and 5-hydroxyindole acetic acid: median eminence (ME), suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), arcuate nucleus (AN), and globus pallidus. In young ovariectomized rats the SCN, MPN, and AN exhibited a diurnal rhythm in 5HT activity which was high during the light hours and low during the dark. The diurnal rhythm could not be detected in any hypothalamic nuclei of ovariectomized middle-aged animals. The loss in the circadian component of 5HT activity is not due to a loss in serotonergic function, since overall turnover rates were not reduced compared to young animals. Estrogen treatment modified the diurnal pattern of 5HT activity in the SCN, MPN, and AN in young rats but had no effect in the middle-aged rats. In young rats, estrogen induced a transitory rise in ME-5HT turnover at 1200 h, just before the expected onset of the LH surge. In middle-aged animals the increase in ME-5HT turnover did not occur until 1800 h and correlates with a delay in the initiation of the estradiol-induced LH surge. We conclude that: 1) there is a loss in the rhythm of 5HT activity in middle-aged rats and 2) the diurnal rhythmicity of 5HT turnover may be necessary for the maintenance of normal cyclic release of LH.

Quantitative assessment of early and discontinuous estradiol-induced effects on ventromedial hypothalamic and preoptic area proteins in female rat brain.

In this study, changes in individual proteins in the ventromedial hypothalamus (VMN) and the preoptic area (POA) of the female rat brain were quantitatively assessed following either a short treatment (2 h) or a discontinuous schedule of estradiol. Ovariectomized (OVX) rats were implanted with estradiol capsules or sham-implanted for the appropriate paradigm and sacrificed by decapitation. Punches of brain tissue containing the VMN and POA were incubated with 35S-methionine and 35S-cysteine, and the labeled proteins separated by two-dimensional gel electrophoresis. Estradiol-induced changes were quantitatively assessed by computerized optical densitometry and subjected to a normalization procedure between pairs of estradiol-treated and OVX control gels. A number of proteins within the VMN and POA were found to be positively or negatively affected in labeling after either hormone administration paradigm. In both brain regions, the population of proteins affected in labeling after 2 h of estradiol treatment were markedly different from those affected after the discontinuous hormone paradigm. Comparison of the VMN and POA also indicated that the populations of proteins affected in labeling by either hormone treatment paradigm were different, with there being only 3 proteins (from a total of 39) affected in the same direction and 2 affected in the opposite direction by the hormone in both regions. These findings lend support to the hypothesis that administration of estradiol results in a molecular cascade of events within brain regions involved in the control of reproductive behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative assessment of the synergistic and independent effects of estradiol and progesterone on ventromedial hypothalamic and preoptic-area proteins in female rat brain.

In this study, quantitative assessment of the synergistic and independent effects of estradiol and progesterone on protein synthesis in the ventromedial hypothalamus (VMN) and the preoptic area (POA) was accomplished using in vitro 35S-methionine and 35S-cystein labeling, two-dimensional gel electrophoresis, and computerized densitometry. Ovariectomized (OVX) rats were divided into four groups. Group 1 was implanted with estradiol (E) capsules for 6 hr and injected with progesterone (P; 0.1 ml, 5 mg/ml propylene glycol) at 20 hr. Group 3 was sham-implanted for 6 hr and injected with 0.01 ml P at 20 hr. Group 4 was sham-planted for 6 hr and injected with vehicle alone at 20 hr. All animals were sacrificed at 24 hr. A number of proteins in both VMN and POA were found to be increased or decreased in labeling by E plus P, E alone, and P alone. Two important synergistic effects of the hormones were found. First, the effects of E on labeling of several proteins in both brain regions were countered by P, and conversely, the effects of P on labeling of several proteins in both brain regions were countered by E. Second, E priming increased the number of proteins affected in labeling by P in both brain regions. Comparison of the effects of E and P on proteins in the VMN and POA indicated that the populations of proteins affected in labeling were markedly different. These results begin to clarify the mechanism in which E and P affect neuronal functioning in two regions involved in the control of reproduction and lend support to the hypothesis that gonadal steroids accomplished their action on brain tissue via a mechanism that is partly unique to the brain region.

Estrogen induces premature luteal regression in rhesus monkeys during spontaneous menstrual cycles, but not in cycles driven by exogenous gonadotropin-releasing hormone.

Administration of exogenous estradiol during the mid- to late luteal phase of the menstrual cycle results in premature regression of the corpus luteum. The present study was initiated to identify the site of action of estrogen as well as to determine why administration of estrogen during the early luteal phase of the menstrual cycle does not result in luteolysis. Based upon extant literature, we hypothesized that estrogen and progesterone synergize to promote premature luteal regression. We tested this hypothesis in intact, spontaneously cycling rhesus monkeys by inserting estradiol, progesterone, or estrogen plus progesterone capsules on days 2 through 6 of the luteal phase. Insertion of estrogen or progesterone capsules alone did not advance luteolysis compared with the effect of control empty implants (n = 3). In contrast, insertion of estrogen plus progesterone implants on days 2 through 6 of the luteal phase resulted in a significant lowering of serum progesterone concentrations, and menses was advanced 5-6 days compared with control cycles. On the basis of these findings in spontaneously cycling monkeys, we speculated that estrogen treatment causes luteal regression only in the presence of a progesterone-mediated decrease in LH pulse frequency. To test this hypothesis, we used rhesus monkeys whose endogenous gonadotropin secretion was abolished by either placement of radiofrequency lesions in the mediobasal hypothalamus or transection of the hypothalamic-pituitary stalk. Ovulatory menstrual cycles were restored by pulsatile administration of exogenous synthetic GnRH. Insertion of estradiol capsules during the luteal phase into animals whose gonadotropin pulse frequency was set at either one pulse per h or one pulse per 8 h failed to cause premature luteal regression (n = 4). These findings indicate that whereas estrogen promotes luteal regression in intact, spontaneous cycling rhesus monkeys, it does not do so in animals whose gonadotropin secretion is controlled by exogenous GnRH. On the basis of these observations, we conclude that the hypothalamus is a major site of action of estrogen in the initiation of luteal regression in macaques.

Effect of oestrogen treatment on gonadotroph function in adult male rats.

The effect of oestradiol-17 beta on the hypothalamo-pituitary axis of intact adult male rats was studied. A single injection of oestradiol did not change the serum LH response to gonadotrophin-releasing hormone (GnRH) 48 h or 7 days after the injection, while administration of oestrogen over 66 days suppressed basal serum LH to less than 3.1 micrograms/l and did not enhance the LH response to GnRH at any time. Treatment of ovariectomized rats with oestradiol capsules, however, enhanced the LH response to GnRH on days 3 and 14 of the treatment as compared with the control group (P less than 0.02 and P less than 0.05 respectively). Long-term treatment with oestradiol suppressed intrapituitary LH and FSH contents as well as pituitary GnRH receptors (P less than 0.0004, P less than 0.005 and P less than 0.001 respectively), whereas serum and intrapituitary prolactin levels were increased. To exclude the possible lactin levels were increased. To exclude the possible inhibitory effect of hyperprolactinaemia on LH were treated with bromocriptine. This prevented the rise in serum prolactin, but failed to enhance the LH response to GnRH. Neither short- nor long-term treatment with oestradiol given under conditions shown to be effective in female animals stimulated the hypothalamo-pituitary-gonadotrophin axis in adult male rats.

Effects of p-chlorophenylalanine on hypothalamic indoleamine levels and the associated changes which occur in catecholamine dynamics and LH surges in estrogen-treated ovariectomized rats

Recent studies have demonstrated that the serotonergic and noradrenergic systems are functionally and anatomically linked and both systems have been implicated as contributors to the regulation of the phasic release of LH. Consequently, perturbations within the serotonergic system could secondarily affect noradrenergic system activity and result in a loss of phasic LHRH secretion. In the present studies we examined the effects of p-chlorophenylalanine (PCPA) on LH surges and the associated changes which occur in hypothalamic serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations. We also evaluated the effects of this drug on norepinephrine (NE) and dopamine (DA) initial concentrations, rate constants and turnover rates in the medial preoptic area (MPN), suprachiasmatic nuclei (SCN), paraventricular nuclei (PVN) and median eminence (ME). Seven days after ovariectomy, rats received estradiol (E 2) capsules (day 0) and on day 1 some animals also received PCPA (250 mg/kg b. wt., i.p.) while the remainder served as controls. LH surges occurred in control animals but not in PCPA-treated rats on days 2, 3 and 4. PCPA produced a significant decline in 5-HT and 5-HIAA concentrations in all microdissected hypothalamic regions at 09.00 and 15.00 h on day 2. In control rats, there were no significant changes in initial concentrations of NE in the MPN, PVN and ME between 09.00 and 15.00 h with the exception of the SCN where a slight decline had occurred by 15.00 h. NE rate constants and turnover rates increased during the afternoon in controls in the MPN, SCN and ME and declined in the PVN concomitant with LH surges. PCPA had variable effects in suppressing NE initial concentrations depending upon the hypothalamic area studied and the time of day. More importantly, the drug abolished the diurnal rhythm in rate constants observed in controls and consequently, neither the MPN, SCN nor ME showed any increase in NE turnover rates in the afternoon of day 2. In contrast, a significant decline in rate constants and turnover rates occurred in the PVN of both control and PCPA-treated rats during the afternoon of day 2. DA initial concentrations declined in controls between 09.00 and 15.00 h in the MPN and ME but not in the SCN or PVN. However, rate constants of DA did not change in any hypothalamic area and, therefore, the decrease in turnover rates in the afternoon in the MPN and ME may not represent an actual decline in DA secretion. In PCPA-treated rats there were no changes in rate constants of DA in any hypothalamic area studied. These data emphasize the importance of evaluating the function of reciprocally innervated neurotransmitter systems when attempting to define a role for a specific neurotransmitter in regulating LHRH release. Since PCPA dramatically suppressed NE rate constants and turnover rates it is not possible to conclude that the reduction of hypothalamic indoleamine concentrations alone caused the loss of LH surges in estrogen-treated rats.

Substance P stimulates gonadotropin-releasing hormone release from rat hypothalamus in vitro with involvement of oestrogen

The effects of substance P on the release of LH and GnRH were examined in a sequential double-chamber perifusion system by perfusing the medio-basal hypothalamus and/or pituitary excised from normal female rats in dioestrus or ovariectomized rats. When the medio-basal hypothalamus and pituitary from normal rats were perifused in series with substance P (10(-6) mol/l), the concentration of LH in the efflux was significantly (P less than 0.05) increased by 70-120% compared with that before the injection, but substance P had no effect on LH release from the pituitary perifused alone. This LH release by substance P increased in a dose-dependent manner and was blocked by substance P antagonist. Administration of 10(-6) mol/l substance P induced a significant release (40-80% increase, P less than 0.05) of GnRH from the medio-basal hypothalamus. Infusion of 10(-6) mol/l substance P induced significant release (50-100% increase, P less than 0.05) of LH and GnRH in ovariectomized rats with an implanted oestradiol capsule, but caused no significant increase in LH release in ovariectomized rats without an oestradiol capsule. Progesterone injection to both ovariectomized rats and ovariectomized rats with an implanted oestradiol capsule had no significant effect on the response of LH to substance P. These findings suggest that substance P induces GnRH release from the medio-basal hypothalamus, resulting in LH release from the pituitary, and that oestrogen may be involved in these processes.

Daily rhythms of serum luteinizing hormone in the immature hamster are estradiol-dependent.

In the female Syrian hamster (Mesocricetus auratus), daily rhythms of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) begin several weeks before regular vaginal estrous cycles are initiated. These rhythms, which appear rather abruptly at about 16 days of age, are dependent on the presence of the ovaries. The experiments described here were intended to determine the nature of the ovarian information required for the initiation and maintenance of the daily LH surge. This surge characterizes the daily cycle of LH and occurs each afternoon at about 1700 h in the intact animal between 2 and 5 weeks of age. Females were ovariectomized at 14 or 15 days of age and implanted with constant-release Silastic capsules of estradiol (E) or progesterone (P). Blood samples were collected at 21 days of age at 1400 or 1700 b, and the serum was assayed for LH, P, and E. While ovariectomy abolished the afternoon surge of serum LH that was observed in sham-operated controls, implantation of E effectively replaced the ovaries. Implantation of P was without effect on LH levels; when P plus E was implanted, the effect was similar to that of E alone. These results suggest that ovaries of the 2-week-old hamster secrete estrogen necessary for the initiation of cyclical LH release.

Effect of catechol estrogens on prolactin secretion in the rat: lack of correlation with estrogenic activity.

Temporal changes in plasma prolactin (PRL) levels caused by the administration of a number of different catechol estrogens to freely-moving conscious male rats were determined. The steroids with a wide range of affinity for the estrogen receptor were given in a single bolus (100 micrograms/kg) into the right atrium via an indwelling cannula. Plasma PRL concentration was monitored by taking blood samples every 2 min. The effect on PRL secretion was found to be more pronounced when the catechol estrogens were administered to rats bearing implants of estradiol and could not be correlated with their Kd values for the estrogen receptor. The synthetic estrogen, diethylstilbestrol, behaved anomalously by producing an elevation in plasma PRL only in estradiol-primed animals or after prolonged infusion. Diethylstilbestrol-treated rats showed no PRL response to 2-hydroxyestrone unlike those bearing Silastic capsules of estradiol. The experiments support the hypothesis that catechol estrogens generally act as short-term dopamine agonists, lowering PRL, but that those which possess estrogenic activity also show a more prolonged PRL-elevating effect. Thus, the overall action of this group of steroids will be determined by factors which influence these two parameters.

Regulation of melatonin's activity in the female rat brain by estradiol: effects on neurotransmitter release and on iodomelatonin binding sites.

The effects of ovariectomy and of 17 beta-estradiol (estradiol) treatment in vivo and in vitro on the ability of melatonin to inhibit dopamine release from the female rat hypothalamus and on [125I]-iodomelatonin binding sites in the brains and hypothalami of female rats were investigated. In long-term (2-4 weeks) ovariectomized (OVX) female rats, the inhibitory effect of melatonin in vitro on dopamine release from the hypothalami was abolished. After implantation of estradiol capsules, the ability of melatonin to inhibit dopamine release from the hypothalamus was reinstated and resembled that observed in intact female rats at estrus and in females exhibiting spontaneous persisting estrus. Similar reinstatement of the responsiveness to melatonin was observed in hypothalami of OVX rats shortly (2 h) after a single subcutaneous injection of estradiol (200 micrograms/animal). Incubation of hypothalami of OVX rats in vitro for 50-90 min with estradiol (0.1-1 nM) resulted in a partial (up to 50%), time and steroid concentration-dependent reinstatement of the ability of melatonin to inhibit the induced dopamine release. Conversely, incubations with estradiol in vitro reduced the ability of melatonin to inhibit dopamine release from the hypothalami of intact rats at proestrus. Such incubations had no effect on the release of dopamine from hypothalami of rats at estrus or of short-term OVX (3 days) rats. The changes in the responsiveness of the hypothalamus to melatonin were accompanied by profound changes in the binding of [125I]-iodomelatonin, to synaptosomes isolated from whole brains and from hypothalami of the OVX female rats. In OVX rats, the densities of the binding sites in the brains and particularly in the hypothalami decreased to 18 and 24% respectively, of the values observed in control females at estrus. The apparent dissociation constant of the remaining sites was significantly lower (ca. 90 nM) than that observed in the intact controls (ca. 300 nM). An almost complete reinstatement of the [125I]-iodomelatonin binding sites was observed in synaptosomes prepared from the hypothalami of OVX rats shortly (2 h) after a single subcutaneous injection of estradiol, or after incubation with estradiol in vitro. The estradiol-mediated reinstatement of [125I]-iodomelatonin binding sites was less pronounced in synaptosomes prepared from whole brains. The results clearly show that estradiol directly modulates the responses of the dopaminergic neurosecretory system in the hypothalamus to melatonin. This phenomenon may be primarily associated with the estradiol-induced changes in the density and function of melatonin receptors in the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Silent ovulation in rhesus monkeys (M. mulatta): Dissociation of hormonal and behavioral states

Ovarian hormone levels were monitored in rhesus monkeys during the breeding and non-breeding seasons. Ovulation (as inferred from progesterone levels in blood serum in excess of 1.5 ng/ml) was most frequent in the breeding season but was absent only during the month of August. Summer (non-breeding season) ovulations were more frequently “silent,” or without heterosexual behavior, than were winter ovulations. This finding suggested that estradiol stimulation may cause different behavioral responses at different times of the year. To test this hypothesis, ovariectomized females were treated with subcutaneously implanted estradiol capsules at different times within and outside the normal breeding season. In either season, treatment with estradiol resulted in increased female-to-female sexual behavior. Only during the breeding season, however, did the estradiol-treated ovariectomized females interact sexually with males. Although males copulated with both estradiol-treated and gonadally intact, untreated females during the breeding season, their rate of copulation with the intact females was higher. The results suggest that: (1) Some female rhesus monkeys displaying strictly seasonal breeding behavior continue to have luteal activity indicative of ovulation in May, June and July, (2) Summer ovulatory cycles are rarely accompanied by sexual behavior, (3) Estradiol treatment of ovariectomized females induces female-to-female sexual behavior both in the breeding and non-breeding seasons, and (4) Males are less responsive to the presence of estrogen-stimulated females in the non-breeding season than in the breeding season.