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PubMed1996

Hypersecretion of follicle-stimulating hormone (FSH) on estrous afternoon in rats treated with RU486 in proestrus.

1. Intact or ovariectomized (OVX) cyclic rats injected or not with RU486 (4 mg/0.2 ml oil) from proestrus onwards were bled at 0800 and 1800 h on proestrus, estrus and metestrus. Additional RU486-treated rats were injected with: LHRH antagonist (LHRHa), estradiol benzoate (EB) or bovine follicular fluid (bFF) and sacrificed at 1800 h in estrous afternoon. LH and FSH serum levels were determined by RIA. 2. RU486-treated intact or OVX rats had decreased preovulatory surges of LH and FSH, abolished secondary secretion of FSH and hypersecretion of FSH in estrous afternoon. The latter was decreased by LHRHa and abolished by EB or bFF. In contrast, EB induced an hypersecretion of LH in RU486-treated rats at 1800 h in estrus. 3. It can be concluded that in the absence of the proestrous progesterone actions, the absence of the inhibitory effect of the ovary in estrus evoked a LHRH independent secretion of FSH.

Animals↗

PubMed1985

Changes of the release of luteinizing hormone (LH) on the day of proestrus after lesions or stimulation of the raphe nuclei in rats.

The effect of stimulation or lesion of the raphe nuclei on ovulation and on the release of luteinizing hormone (LH) on the day of proestrus was studied in unanesthetized, unrestrained rats. Electrochemical stimulation (anodic DC or 100 microA during 30 s) was applied at 12.00 h on the day of proestrus through chronically implanted stainless steel electrodes. Lesions were made by passing a cathodic current of 1 mA for 20 s through nichrome electrodes stereotaxically implanted and the rats were used 15-30 days later. Blood samples were obtained hourly from the freely behaving rats through a plastic cannula inserted into the external jugular vein. Stimulation in the medial raphe nucleus (MRn) resulted in blockade of ovulation and of the preovulatory LH release. On the contrary, no change of the normal pattern of LH surge nor in the number of ovulating rats was seen after stimulation of the dorsal raphe nucleus (DRn) or in rats stimulated in the mesencephalon outside these nuclei. Injection of p-chlorophenylalanine (PCPA) into the MRn to block 5-hydroxytryptamine (5-HT) synthesis, prevented the effect of MRn stimulation, whereas injection of saline solution did not. Rats bearing lesions destroying the DRn showed decreased proestrous LH surge and blockade of ovulation whereas those with lesions of MRn ovulated normally. Rats with transverse cuts placed just behind the DRn exhibited normal LH release indicating that the effects of destroying the DRn is not due to the interruption of ascending fibers crossing the nucleus. Injections of PCPA in the DRn but not saline solution mimicked the effect of lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Corticotropin releasing hormone mRNA is elevated on the afternoon of proestrus in the parvocellular paraventricular nuclei of the female rat.

We investigated changes during the estrous cycle in cellular levels of corticotropin-releasing hormone (CRH) mRNA in parvocellular neurons of the hypothalamic paraventricular nucleus, using in situ hybridization. Intact female rats with 4 day cycles were sacrificed at 11 different times during the cycle at 09.00 h and 16.00 h on each day, with additional collection times at 14.00 h, 18.00 h, and 20.00 h on the day of proestrus. Twelve microns coronal sections of fresh-frozen brains were made through the paraventricular nuclei (PVN) and placed on gelatin-coated slides. A 48 base oligodeoxynucleotide probe complementary to the coding region for rat CRH was used to measure CRH mRNA. There was a sharp increase (P less than 0.01) in CRH mRNA in the ventral PVN between 14.00 and 16.00 h on the day of proestrus, at the approximate time of the ovulatory surge. Following this rise, there was an even larger decline (P less than 0.01) between P 16.00 h and P 20.00 h. Levels of CRH mRNA did not change greatly on other days of the cycle, nor were there significant changes in the dorsal PVN. Given the known effects of CRH on GnRH secretion, these changes occur at a time when they could serve to modulate the midcycle luteinizing hormone (LH) surge.

Animals↗

PubMed1997

Fertility impairment after mifepristone treatment to rats at proestrus. Actions on the hypothalamic-hypophyseal-ovarian axis.

Accumulated evidence indicates that the antigestagen mifepristone affects the reproductive axis acting on hypothalamic, pituitary, ovarian, and uterine tissues. The purpose of this study was to further investigate which reproductive functions are impaired by the antagonist, critically compromising the reproductive process, leading to unsuccessful pregnancy. Circulating pituitary and ovarian hormones, sexual receptivity, ovulation, and implantation rates were studied in cycling rats receiving a single dose of mifepristone (1 or 10 mg/kg subcutaneously) at 12:00 proestrus, before luteinizing hormone (LH) stimulation of the ovulatory process. Mifepristone-treated rats had decreased preovulatory surges of LH and prolactin (PRL), and hypersecretion of LH, PRL, and progesterone at estrus. The sexual receptivity was dramatically affected by the antagonist as indicated by the profound decrease in the lordosis response evaluated on the night of proestrus. The number of ovulating animals and the number of oocytes recovered from the oviduct on the morning of estrus were not affected by mifepristone. The low number of rats that succeeded in mating with potent males became pregnant. However, they delivered an average of only two pups at parturition, indicating a failure in the implantation of the fertilized ova, as ovulation was not affected by the antagonist at the dose used. We conclude that a dramatic inhibition of the sexual receptivity and unsuccessful implantation, preceded by a reduction on LH and PRL secretion, are the major components leading to fertility impairment after a single dose of mifepristone administered before the preovulatory surge of LH.

Animals↗

PubMed2002

Proestrus levels of estradiol during transient global cerebral ischemia improves the histological outcome of the hippocampal CA1 region: perfusion-dependent and-independent mechanisms.

We conducted this study to determine whether high physiological levels of estradiol (proestrus) could protect the hippocampal CA1 neurons following transient global ischemia. Ovariectomized or ovary-intact female rats were subjected to 20 min of ischemia and allowed to survive for 96 h. Estradiol was administered subcutaneously in a group of ovariectomized rats 24 h before ischemia induction. Ending serum estrogen levels were correlated to cerebral blood flow (CBF), histologic assessment and immunofluorescent caspase-3 active peptide (C-3AP) positive cell count. Estradiol administration significantly improved CBF in the hippocampus (compared with intact or ovariectomized rats) but not in the parietal cortex. No significant differences in CBF between intact or ovariectomized rats were noted. Estradiol administration maintained serum levels of the steroid in estradiol-treated rats-about 10 times that of intact animals and more than 20 times that of ovariectomized animals. Morphologically, live cell counts in estradiol-treated rats were significantly higher than in intact or ovariectomized rats. Live cell counts were also significantly higher in intact than ovariectomized rats. C-3AP positive cell counts were much higher in ovariectomized rats than in intact and estradiol-treated rats. In conclusion, proestrus levels of 17beta-estradiol protect hippocampal CA1 neurons against transient global ischemia, through mechanisms that appear to involve improvement of perfusion and inhibition of caspase-3 activity.

Animals↗

PubMed1980

Effect of exogenous hormones on the activity of delta 5,3 beta-hydroxysteroid dehydrogenase in cultured granulosa cells from proestrus and preovulatory rat ovarian follicles.

Activity of delta 5,3 beta-hydroxysteroid dehydrogenase (delta 5,3 beta-OH SD) in cultured granulosa cells isolated from rat ovarian follicles at various hours of proestrus was histochemically investigated. Control cultures as well as cultures with addition of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, and estradiol were carried on. In control cultures activity of the enzyme followed more or less the pattern observed in vivo. Exogenous LH added during preovulatory LH surge showed additive effect on enzyme activity. Other hormones stimulated enzyme activity on the morning of proestrus and at the time close to ovulation, when prolactin exerted most stimulatory effect.

3-Hydroxysteroid Dehydrogenases↗

PubMed2006

Reproductive experience reduces circulating 17beta-estradiol and prolactin levels during proestrus and alters estrogen sensitivity in female rats.

The reproductive experiences of pregnancy, parturition, and lactation affect a range of neural and endocrine processes after the end of lactation. In women, previous parity results in reduced circulating prolactin (PRL) and androgen levels years after giving birth. Reductions in PRL secretion also occur in reproductively experienced, female rats. In the present study we examined the status and regulation of estradiol (E(2)) and PRL during the reproductive cycle after reproductive experience. These hormones regulate one another and have been implicated in a number of disease and aging processes. Using a rat model, the patterns of E(2) and PRL secretion, pituitary PRL content, and estrogen receptor alpha expression were characterized from 1200-1800 h on proestrus in age-matched, primiparous and nulliparous animals. The possible effect of parity on estrogen sensitivity was then examined by challenging nonlactating, ovariectomized, age-matched, multiparous and nulliparous rats with estradiol benzoate (EB; 0, 1, 5, 25, and 125 microg/kg) and measuring PRL responses 24 and 48 h later. Previous parity resulted in modest, yet significant, reductions in E(2) and PRL levels on proestrus, a limited increase in pituitary estrogen receptor alpha expression, and a significant shift in estrogen sensitivity, as measured by EB-induced PRL secretion. Nulliparous animals were more sensitive than multiparous rats to the two lower doses of EB, whereas multiparous animals were more responsive to the highest EB dose. These unique parity-induced alterations in the female's endocrine state that persist beyond lactation may impact a multitude of estrogen-mediated processes over the female's adult life span.

Animals↗

PubMed1983

Changes in somatostatin-like activity in discrete areas of the rat hypothalamus during different stages of proestrus and diestrus and their relation to serum gonadotropin, prolactin, and growth hormone levels.

To investigate physiological changes in the somatotropin release-inhibiting factor (SRIF) content of the hypothalamus during the estrous cycle, groups of 8-10 rats were decapitated every 2 h from 0800-1800 h on proestrus and diestrus. SRIF was assayed in the preoptic suprachiasmatic area, posterior hypothalamus, arcuate nucleus area, and median eminence. Gonadotropins, PRL, and GH were measured in trunk blood and correlated with concentrations of SRIF. A marked decrease in SRIF occurred between 0800-1400 h of proestrus in the preoptic suprachiasmatic area (1.00 +/- 0.28 vs. 0.09 +/- 0.03 micrograms/g wet wt, P less than 0.001) and the posterior hypothalamus (0.43 +/- 0.10 vs. 0.02 +/- 0.004 micrograms/g, P less than 0.001). A similar pattern of decrease in SRIF also occurred in the tissue containing the arcuate nucleus (2.09 +/- 0.37 vs. 0.98 +/- 0.13 micrograms/g, P less than 0.01). In the median eminence the lowest SRIF concentration was measured at 1600 h (31.4 +/- 3.4 vs. 22.0 +/- 1.32 micrograms/g, P less than 0.02). Diestrous values for SRIF did not change in the posterior hypothalamus and arcuate area; however, values increased slightly in the median eminence and decreased in the preoptic suprachiasmatic area between 1400-1800 h. Spearman's correlation coefficient (rs) between PRL and SRIF in the preoptic suprachiasmatic area and the posterior hypothalamus was rs = -0.66 and rs = -0.55 (P less than 0.001), respectively.

Animals↗

PubMed1996

Decreased gonadotropin-releasing hormone neurosecretory response to glutamate agonists in middle-aged female rats on proestrus afternoon: a possible role in reproductive aging?

Before becoming acyclic, middle-aged rats display an attenuated LH surge and a decreased number of activated GnRH neurons. The present study examined whether the decreased activation of GnRH neurons in middle-aged rats could be due to defective glutamate neurosignaling in the hypothalamus. Arcuate nucleus/median eminence (ARC/ME) fragments were isolated from young (2-month-old) and middle-aged (9- to 11-month-old) rats at 1700 h on proestrus and incubated in vitro with or without the specific glutamate agonists, D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (1 mM), kainate (1 mM), and N-methyl-D-aspartate (NMDA; 50 mM). The results showed that basal GnRH release was similar in the two age groups. In contrast, stimulated GnRH release by D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate, and NMDA was significantly attenuated in middle-aged vs. young rats. KCl stimulation at the end of the experiments confirmed the viability of all ARC/ME fragments. Quantitative reverse transcriptase-PCR revealed that messenger RNA levels for the major NMDA receptor subunit (NMDAR1) were significantly lower in the preoptic area and ARC/ME of the middle-aged rat on proestrus afternoon. As a whole, these findings suggest that a defect in hypothalamic glutamate neurosignaling may be an important mechanism leading to age-related defects in LH secretion and acyclicity in female animals.

Aging↗

PubMed1996

The brain histamine (HA) and pituitary luteinizing hormone (LH) levels in female rats anesthetized with ether on proestrus.

Levels of brain histamine (HA) and pituitary luteinizing hormone (LH) were determined in female rats anesthetized with ether in the afternoon of proestrus. The rats after 6-hr ether anesthesia had an average HA concentration higher than that of non-anesthetized rats in the hypothalamus, but not in the cortex or diencephalon. Ether-anesthetized rats also showed a higher LH level in the pituitary than that of non-anesthetized rats. These findings agree well with our previous observation of an inhibited ovulation associated with a decrease in serum LH in female rats anesthetized with ether in the afternoon of proestrus. Furthermore, it is suggested that the release of pituitary LH into the circulating blood is regulated by the level of HA in the hypothalamus.

Anesthesia↗

PubMed1992

Prolonged proestrus in a bitch with X chromosomal monosomy (77,XO).

A stunted Miniature American Eskimo bitch that had signs of proestrus, which persisted for almost 8 months, had a 77,XO karyotype. Despite signs of proestrus, the ovaries were small and fibrous, and there was no evidence of ovarian follicle development or corpora lutea. Except for its juvenile appearance, the rest of the reproductive tract was grossly normal. Clinical signs in this bitch were similar to those in human beings with Turner's syndrome.

Animals↗

PubMed1984

Concentrations of testosterone in canine serum during late anestrus, proestrus, estrus, and early diestrus.

Serum testosterone concentrations in samples collected daily from 6 bitches for at least 60 days before the onset of diestrus were determined by radioimmunoassay. Mean serum concentrations (+/- SEM) of testosterone ranged from 31 +/- 11 to 141 +/- 63 pg/ml during late anestrus. Mean testosterone concentrations during proestrus ranged from 106 +/- 29 to 239 +/- 113 pg/ml, with the highest concentration (526 +/- 225 pg/ml) occurring the day of the preovulatory surge of luteinizing hormone. Although the ovaries may be sites of production during late anestrus, proestrus, estrus, and early diestrus, further investigation is necessary to determine whether testosterone has an important physiologic or endocrinologic function in the bitch (ie, sexual behavior, vaginal hypertrophy, and luteinizing hormone surge).

Anestrus↗

PubMed1994

Use of Fos-related antigens (FRAs) as markers of neuronal activity: FRA changes in dopamine neurons during proestrus, pregnancy and lactation.

This manuscript describes the use of staining of Fos-related antigens (FRAs) as markers for changes in neuronal activity. The model system consisted of the tuberoinfundibular dopamine (TIDA) neurons located in the arcuate nucleus of the hypothalamus. Under normal conditions, these neurons are devoid of c-Fos staining even though the neurons are tonically active and can express FRAs. During specific neuroendocrine states the neurons undergo changes in activity, as described by other studies. At times when the activity is relatively high as in pregnancy and during proestrus, approximately 50%-60% of the TIDA neurons expressed FRA immunoreactivity. Moreover changes over the course of proestrus paralleled known shifts in TIDA activity (declining as the day progressed). At times when TIDA activity is suppressed, such as during lactation, FRA staining in TIDA neurons was markedly reduced or absent. Upon removal of the suckling stimulus, FRA staining rose to reach peak expression 12-24 h after pup removal (without coordinate induction of c-Fos). These data suggest that FRA staining can serve as a useful marker of activity in the TIDA neurons which permits not only assessment of stimulated activity but also suppressed function in the neurons. A cautionary note in using this approach along with acquisition of serial blood samples for hormone measurement is that surgical procedures for monitoring plasma hormone levels are associated with strong long-lived induction of FRAs (and c-Fos) in many neurons (including the TIDA neurons) that can confound interpretation of FRA staining.

Analysis of Variance↗

PubMed1988

Analysis of estradiol-independent and -dependent endogenous opioid peptide suppression of pulsatile LH release between the mornings of diestrus 2 and proestrus in the rat estrous cycle.

The aim of this study was to analyze possible estradiol (E2)-independent and -dependent endogenous opioid peptide (EOP) suppression of pulsatile LH release between the mornings of diestrus 2 (D2) and proestrus by examining the LH response to naloxone infusions in the presence or absence of proestrous levels of E2. Pulsatile LH secretion remained unchanged between D2 and proestrus but mean blood LH levels, pulse amplitude and frequency increased within 24 hr following ovariectomy on D2. This increase was due in large part to the loss of E2 negative feedback, since restoration of physiological proestrous E2 levels returned LH pulse frequency to proestrous a.m. levels and greatly reduced pulse amplitude. In ovariectomized rats lacking E2 negative feedback, continuous infusion of the EOP receptor antagonist naloxone (0.5 and 2 mg/kg/hr) caused a further increase in pulse amplitude and frequency. This naloxone-induced increment in pulsatile LH release was exerted via centrally located EOP receptors since naloxone did not alter pituitary responsiveness to LHRH, and its stimulatory action on pulsatile release was diminished by simultaneous infusion with morphine. Naloxone also increased pulsatile LH release in E2-treated animals. The naloxone-induced increments in LH pulse amplitude were the same in the presence or absence of E2 negative feedback. Moreover, the increments in amplitude produced by naloxone in E2-treated rats were significantly less than those resulting from the combination of ovariectomy plus naloxone infusion in empty capsule-implanted rats. These data indicated that naloxone infusion in E2-implanted animals blocked an E2-independent EOP suppression of this parameter of pulsatile release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1979

Inhibition of estrous cyclicity in golden hamsters by melatonin administration on the day of proestrus.

Single injections of melatonin (25 micrograms) were administered to female hamsters, 15 minutes before lights-out (14L:10D), during either the early diestrous (day 1) or proestrous (day 4) phase of the estrous cycle. Hamsters which received melatonin only on the evening of proestrus became anovulatory by three weeks of treatment, while those that were injected with melatonin during diestrus, or administered oil on either day 1 or 4, continued to exhibit normal estrous cycles. These results indicate that quartan injections of melatonin can suppress reproductive function in female hamsters, and that the effectiveness of the injections may be dependent upon the stage of the estrous cycle at which they are administered.

Animals↗

PubMed1984

Myometrial responses in situ to nicergoline, acebutolol, phentolamine and noradrenaline of the rat in proestrus.

The effects of two adrenoceptor antagonists, nicergoline (alpha 1) and acebutolol (beta 1), on the contraction of myometrium in the proestrous rat were compared to those of noradrenaline and phentolamine. The spontaneous myometrial contractions of Wistar rats on the day of proestrus were recorded isometrically and the data were analysed using Wilcoxon non-parametric statistics. All drugs were administered i.v. and the doses are expressed as microgram/kg body weight. Noradrenaline (1200 micrograms/kg per h) induced a 32.5% reduction (P less than 0.001) of the uterine contraction amplitude. Nicergoline did not alter uterine motility significantly when administered alone at doses ranging from 400 to 1600 micrograms/kg. However, successive injections of nicergoline in the same range given during noradrenaline infusion at 600 micrograms/kg per h potentiated the relaxing action of the latter (38%, P less than 0.01). Phentolamine (120 micrograms/kg) reduced myometrial activity by 25% (P less than 0.05). This inhibitory response rose to 65% (P less than 0.001) when the dose of phentolamine was increased to 960 micrograms/kg. When a single injection of nicergoline (400 micrograms/kg) was followed by the administration of increasing doses of acebutolol (120, 1200, 2400 micrograms/kg) the slight inhibitory effect on uterine motility observed after administration of each of the two agents separately became more pronounced (P less than 0.05). It appears from these results that combining noradrenaline with nicergoline and nicergoline with acebutolol leads to potentiation of their relaxing effects. Furthermore the results confirm that nicergoline is a partial alpha-blocker.

Acebutolol↗

PubMed1989

Serotonin binding sites during proestrus and following estradiol treatment.

The binding of 3H-5-HT to hypothalamic, hippocampal and striatal membranes from female rats was examined. During the day of proestrus, there was a significant increase in binding from morning to evening. The increase reflected changes in both Kc and Bmax. Effects of estradiol were examined in ovariectomized rats, and changes in 3H-5-HT binding resulted from an increase in the Kd after estradiol treatment. These in vivo effects of estradiol were not seen when tissue was incubated in vitro with estradiol. However, the compound, polyvinylpyrrolidone, used in the in vitro incubation significantly increased the Kd for binding to 3H-5-HT and estradiol attenuated the increase. The potential significance of these changes to serotonin's modulation of reproductive function is discussed.

Animals↗

PubMed1985

Immunoreactive substance P and LH-RH content in median eminence and pituitary gland during proestrus, oestrus, lactation and after anterior hypothalamic deafferentation.

Substance P (SP) and luteinizing hormone releasing hormone (LH-RH) content were measured by radioimmunoassay in median eminence of female rats, SP only in rats pituitary after decapitation on the day of oestrus (E), on the first and second day of dioestrus (D1 and D2), on the day of proestrus (P) and in "constant oestrus" (AD) caused by anterior hypothalamic deafferentation and in lactation (L). During four days of oestrus cycle the highest SP and LH-RH content of median eminence was found in dioestrus. Both during cyclic oestrus and "constant oestrus", SP and LH-RH were significantly lower than on the second day of dioestrus. These results may suggest the reciprocal functional relation of both hypothalamic peptides in the mechanism of the control of gonadotropin release. The highest LH-RH concentration of the median eminence was found in the animals on the 11th to 15th day of lactation, while the SP content in the median eminence of these animals is not significantly different from those of the remaining groups except the value for dioestrus (D2) rats. The SP content in pituitary of lactating rats was significantly higher than those of rats during cyclic or "constant oestrus".

Animals↗