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PubMed1998

C-fos expression pattern in the hypothalamus and the preoptic area of the rat during proestrus.

c-fos gene expression in the hypothalamus, the preoptic area, the hippocampus and the frontal cerebral cortex of the rat was determined every two hours from 09:00 h to 19:00 h on the day of proestrus by using reverse transcription coupled to polymerase chain reaction. Rats under a 14:10 h light-dark cycle, with lights on at 06:00 h were used. We found a marked increase in c-fos gene expression in the studied regions but the hippocampus at 13:00 h, followed by a significant diminution in the subsequent hours of proestrus day. The high expression of c-fos gene at 13:00 could be associated to the increase in estradiol seric levels observed both at 11:00 h and at 13:00 h. Our results correlate with the increase in the number of FOS immunoreactive cells in some forebrain areas in proestrus afternoon related to gonadotropin releasing hormone secretion.

Animals↗

PubMed1986

Catecholamines in sow graafian follicles at proestrus and at diestrus.

Endogenous dopamine, noradrenaline, and adrenaline were detected in the sow graafian follicular wall and in the follicular fluid. Noradrenaline represented the highest level and adrenaline the lowest. Dopamine and noradrenaline concentrations found in the follicular fluid were lower at early proestrus than at mid-diestrus, whereas adrenaline levels in the fluid did not differ at either stage of the estrous cycle. The sow follicular wall contained less dopamine, noradrenaline and adrenaline at early proestrus than at mid-diestrus. Concomitantly, a decrement of [3H]-dopamine and [3H]-noradrenaline uptake, and of dopamine-beta-hydroxylase activity was detected at early proestrus compared to levels detected at mid-diestrus. The findings in sow graafian follicles show the existence of relationships between hormonal status, dopamine, noradrenaline and adrenaline endogenous levels and uptake, and dopamine-beta-hydroxylase activity. Possible links between estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels during the pig estrous cycle and ovarian catecholamines are discussed, as is a plausible involvement of these neurotransmitters in the contractile activity of the theca layer and the processes of follicular rupture and ovulation.

Animals↗

PubMed1998

Both prolactin and progesterone in proestrus are necessary for the induction of apoptosis in the regressing corpus luteum of the rat.

This study was conducted to analyze the roles of prolactin (PRL) and progesterone in the induction of luteal cell apoptosis and accumulation of macrophages in the regressing corpus luteum. We studied the number of apoptotic cells and macrophages in regressing corpora lutea in estrus 1) in cycling rats or after blocking PRL secretion with the dopaminergic agonist CB154, and 2) after blocking progesterone actions with the progesterone receptor antagonists RU-486 or ZK98299. Cells showing the morphological features characteristic of apoptosis contained fragmented DNA as indicated by in situ 3' end labeling. In cycling rats, a 100-fold increase in the number of apoptotic cells and a 4-fold increase in the number of macrophages was found from the evening (1600 h) of proestrus to the morning (1100 h) of estrus. Both increases were blocked by PRL suppression with CB154. Furthermore, blocking progesterone actions with progesterone receptor antagonists RU-486 or ZK98299 without affecting PRL secretion inhibited apoptosis but did not affect the accumulation of macrophages, whether treatment was started on the morning of metestrus (blocking diestrous and proestrous progesterone) or on proestrus (blocking only proestrous progesterone). Otherwise, exogenous progesterone was not effective in inducing apoptosis in the absence of PRL. These results indicate that both PRL and progesterone in proestrus are necessary for the induction of apoptosis in the regressing corpora lutea, whereas the accumulation of macrophages seemed to be dependent exclusively on the PRL surge.

Animals↗

PubMed1997

Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males.

OBJECTIVES: To determine: a) whether the cell-mediated immune response during sepsis differs in females vs. males; and b) whether the survival rate in females is different than in males after a septic insult. DESIGN: A prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female proestrus C3H/HeN mice. INTERVENTIONS: After anesthesia, male and proestrus female mice underwent cecal ligation puncture to induce sepsis. The mice were killed at 24 hrs after the onset of sepsis. MEASUREMENTS AND MAIN RESULTS: Splenocyte proliferation, as well as splenocyte interleukin (IL)-2 and IL-3 release, was determined by bioassay. In additional studies, survival rate after septic challenge was measured over 10 days. Splenocyte proliferative capacity and splenocyte IL-2 and IL-3 release were markedly decreased in male, but not in female, septic mice. Furthermore, the survival rate of septic female proestrus mice was significantly higher than in comparable male mice. CONCLUSIONS: These results support the concept that the immune response of females differs from males, and that females are immunologically better positioned to meet the challenge of sepsis.

Adolescent↗

PubMed2003

Improved survival in uncontrolled hemorrhagic shock induced by massive splenic injury in the proestrus phase of the reproductive cycle in the female rat.

Estrogen has a protective effect in adverse circulatory conditions such as trauma-hemorrhage and ischemia-reperfusion. In the present investigation uncontrolled hemorrhagic shock induced by massive splenic injury (MSI) was studied in male and female rats during the proestrus and metestrus phase of the reproductive cycle. The animals were anesthetized and randomly divided into four groups: group 1 (n = 8) were sham operated female animals; in group 2 (n = 8) MSI was induced in male animals; in group 3 (n = 8) MSI was induced in female animals in proestrus; in group 4 (n = 8) MSI was induced in female animals in metestrus. Plasma 17beta-estradiol was 112.8 +/- 16.7 pg/mL in group 3 and 44.8 +/- 16.7 pg/mL in group 4 (P < 0.04). After MSI the mean arterial pressure dropped in group 2 from 135.6 +/- 3.9 to 47.6 +/- 8.8 mmHg (P < 0.001) in 60 min. Total blood loss in 4 h was 29.6 +/- 3.5% of blood volume and mean survival time 161.3 +/- 30.6 min. In group 3 total blood loss in 4 h was 24.4 +/- 5.7% of blood volume and mean survival time 240 +/- 0 min (P < 0.03 compared with group 2). In group 4, total blood loss in 4 h was 29.6 +/- 3.9% of blood volume and mean survival time was 112.3 +/- 28.7 min (P < 0.001 compared with group 3). These results indicate that female rats in the proestrus phase of the reproductive cycle better maintain hemodynamic stability and survival in uncontrolled hemorrhagic shock than female animals in metestrus or males. This difference is attributed to factors other than blood loss.

Animals↗

PubMed2003

Immunomodulatory effects of dehydroepiandrosterone in proestrus female mice after trauma-hemorrhage.

Studies indicate that administration of the adrenal steroid dehydroepiandrosterone (DHEA) after trauma-hemorrhage in male mice improved cellular immune functions and reduced mortality rates from subsequent sepsis. There is evidence, however, that DHEA is converted to estrogens in males and that estrogens are immunoprotective after trauma-hemorrhage (TH). In contrast, DHEA in females can be converted to testosterone that has deleterious effects on immune functions. The aim of our study, therefore, was to determine whether administration of DHEA in proestrus females after TH would deteriorate immune responses. Proestrus female C3H/HeN mice (age 7-8 wk) were subjected to laparotomy (i.e., soft tissue trauma induced) and hemorrhagic shock (35 +/- 5 mmHg for 90 min) or sham operation. The mice then received DHEA (100 micro/25 g body wt) or vehicle subcutaneously followed by fluid resuscitation (4x the shed blood volume). Plasma IL-6, splenocyte proliferation, splenocyte IL-2, IL-3, IFN-gamma, IL-10 release, and splenic Mphi IL-1beta, IL-6, IL-10, and IL-12 release were determined 24 h after TH. Plasma IL-6 levels were significantly increased in vehicle-treated females, and DHEA administration markedly attenuated this response. In vehicle-treated females, splenocyte proliferation, IL-2, IL-3, and IFN-gamma release, and splenic Mphi IL-1 beta, IL-6, and IL-12 release were maintained or slightly enhanced after TH. In DHEA-treated females, however, these immune functional parameters were either unaltered compared with vehicle-treated animals or even further enhanced, but surprisingly were not depressed. Moreover, DHEA reduced splenocyte and splenic M phi anti-inflammatory cytokine (i.e., IL-10) production after TH compared with vehicle-treated females. Because DHEA further enhances the immune responsiveness in proestrus females after TH, this hormone might be a useful adjunct even in females for further enhancing immune responses and decreasing the mortality rate after trauma and severe blood loss.

Adjuvants, Immunologic↗

PubMed2001

Diazepam increases the number of punished responses in a conflict-operant paradigm during late proestrus and estrus in the Wistar rat.

Both anxiety-like behavior and the response to anxiolytic drugs vary according to the estrus cycle in the rat. Consequently, anxiety-like behavior and the sensitivity to anxiolytic drugs may be related to hormone level fluctuations occurring during the estrus cycle. In male rats tested in a conflict-operant paradigm, anxiolytic drugs increase immediate punished responding. However, it is unknown whether estrus phases impinge on the immediate punished responses in a conflict-operant paradigm. Therefore, in this study female rats were trained in a conflict-operant paradigm; after training all animals received vehicle or diazepam. Then the number of immediate punished reinforcers was evaluated during the estrus cycle. Results showed that vehicle-treated rats evaluated during late proestrus and estrus obtained a higher (p < 0.05) number of immediate punished reinforcers than rats evaluated during metestrus and diestrus. A low dose of diazepam (1.3 mg/kg; i.p) significantly increased (p < 0.05) the immediate punished responses only in late proestrus and estrus. The highest dose of diazepam tested (2.0 mg/kg; i.p.) significantly increased (p < 0.05) the immediate punished reinforcement in any estrus phase. These results suggest that a lower level of anxiety-like and an increased sensitivity to an anxiolytic drug occurred only in late proestrus and estrus in rats tested in a conflict-operant paradigm.

Animals↗

PubMed1975

Role of brain monoamines in release of gonadotropin before proestrus in the cyclic rat.

To determine whether brain monoaminergic neurons are involved in the release of gonadotropins responsible for estrogen increases before proestrus, various inhibitors and precursors of monoamine biosynthesis were administered subcutaneously or intracranially to the 3rd ventricle at 10.00 or 20.00 on the day before proestrus, the 2nd day of diestrus (DII) in 4-day cycling rats. The inhibitors used were alpha-methyl-p-tyrosine (alpha-MPT) and bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)-disulfide (FLA-63). The effects of these drugs on changes in vaginal cytology, ovulation, uterine weight of uterine intraluminal fluid, and on serum concentrations of LH and FSH were evaluated in selected experiments. (1) Administration of alpha-MPT (150 mg/kg s.c.), an inhibitor of tyrosine hydroxylase, at 10.00 on DII reduced weights of uterus and intraluminal fluid on the day of expected proestrus (P), prevented vaginal cornification on estrus (E), blocked ovulation in all 10 rats, and induced prolonged diestrus. (2) Administration of FLA-63 (10 mg/kg s.c.), an inhibitor of dopamine-beta-hydroxylase, at 10.00 on DII reduced weights of uterus and intraluminal fluid on P, blocked ovulation for a few days but did not prevent vaginal cornification at the expected time of E. (3) Administration of alpha-MPT (200 mg/kg) or FLA-63 (15 mg/kg) at 20.00 on DII blocked ovulation in all of 8 and 7 rats, respectively, but these treatments did not block vaginal cornification at the expected time in any animal. (4) Administration of L-DOPA (100 mg/kg) or dihydroxy-phenylserine (DOPS, 200 mg/kg) with alpha-MPT (200 mg/kg) at 20.00 on DII reversed the blocking effect of alpha-MPT on ovulation in 3 out of 6 and 3 out of 5 rats, respectively. (5) Direct application of crystalline alpha-MPT or FLA-63 (about 3-5 mug) to the 3rd ventricle at 20.00 on DII also blocked ovulation in all of 7 and 5 rats, respectively. (6) Both systemic and intraventricular injections of alpha-MPT at 10.00 on DII reduced serum LH on P but not serum FSH. FLA-63 by intraventricular injection also reduced serum LH but not serum FSH. (7) Injection of 17beta-estradiol (40 mug s.c.) with alpha-MPT or FLA-63 partially removed the ovulatory blockade induced by conditions 1, 2, 3 and 5. Therefore, norepinephrine seems to be an important neurotransmitter in the release of gonadotropin responsible for estrogen secretion before P, but dopamine may also be involved during its early stage as represented by 10.00 on DII.

Animals↗

PubMed1982

Correlative surges of LHRH, LH and FSH in pituitary stalk plasma and systemic plasma of rat during proestrus. Effect of anesthetics.

An effective recovery procedure has been utilized for determining luteinizing hormone-releasing hormone (LHRH) concentrations in rat pituitary stalk plasma. With this new recovery protocol it was revealed that stalk plasma immunoreactive LHRH concentrations increased 5-fold to 206 pg/ml during proestrus(p less than 0.001) and decreased to diestrous levels during estrus. In contrast, the LHRH concentration in systemic plasma extracts remained unchanged throughout the estrous cycle and did not exceed 4 pg/ml. The stalk plasma: systemic plasma ratio increased from 12:1 at diestrus to 76:1 at proestrus; it then decreased to 22:1 at estrus (p less than 0.001). Correlative luteinizing hormone (LH) and follicle-stimulating hormone (FSH) surges of statistically significant magnitudes were observed in the systemic plasma of nonanesthetized cardiac-catheterized rats during proestrus. When administered before the onset of the critical period, Althesin and other anesthetic agents suppressed but did not completely inhibit the peripheral LH surge in cardiac-catheterized rats. The FSH surge was suppressed also but to a lesser degree. These results indicate that the brain triggers the preovulatory surge of LH and FSH via massive secretion of LHRH into the pituitary portal circulation. They also reveal that, aside from any dosage considerations, the type of anesthetic used and the time of administration in relation to the critical period, can significantly affect the magnitude of pituitary LH and FSH secretion.

Anesthetics↗

PubMed1984

Median eminence serotonin involved in the proestrus gonadotropin release.

Numerous studies have suggested that serotonin (5-HT) is involved in the regulation of anterior pituitary hormone release. In the present study, the 5-HT concentrations of the median eminence and anterior pituitary lobe were measured during the estrous cycle and lactation in order to correlate changes in 5-HT levels with changes in serum luteinizing hormone, follicle-stimulating hormone, and prolactin. On the day of proestrus, median eminence 5-HT concentrations declined significantly between 14.00 and 16.30 h at the beginning of the gonadotropin and prolactin surges. No changes in 5-HT concentrations were found between the morning and afternoon on other days of the cycle. In the anterior pituitary, the levels of 5-HT did not change during the estrous cycle. 5-HT turnover rates were also estimated in the median eminence on proestrus and diestrus 1. The median eminence 5-HT synthesis rate increased in the afternoon of proestrus at 16.30 h. 5-HT was also measured in the anterior pituitary and the median eminence of lactating rats in four experimental situations: mothers with their litter until decapitation, mothers separated from their pups 4 h earlier, and mothers separated from their pups 4 h earlier, after which the pups were allowed to suckle for 5 or 30 min. In spite of the acute changes in circulating prolactin, 5-HT levels in the median eminence were not affected in any situation studied. These results suggest that 5-HT in the median eminence is involved in the control of gonadotropin release. The data further suggest that 5-HT does not act directly on the anterior pituitary to modulate gonadotropin or prolactin release.

Animals↗

PubMed1986

Interaction between estradiol and a nonsteroidal factor in porcine follicular fluid in regulating LH pulse amplitude between the mornings of diestrus 2 and proestrus in the rat.

The object of this study was to examine the effect of porcine follicular fluid (PFF) alone or in combination with estradiol (E2) on pulsatile LH release during the interval between the mornings of diestrus 2 (D2) and proestrus in the rat. Steroids were removed from PFF by charcoal extraction. Preliminary studies indicated that 1 ml PFF given intraperitoneally suppressed FSH secretion for up to 15 h, with an onset of action between 3 and 4 h and maximal suppression between 6 and 9 h. In subsequent experiments, six groups of animals were bled continuously for 3 h between 07.30 and 10.30 h at a rate of 50 microliter whole blood/5 min: group 1 was bled on D2; group 2 was sham ovariectomized on D2 (08.30-09.30 h), immediately implanted with an empty capsule, given saline at 12.00 and 24.00 h, and bled on proestrous AM; groups 3-6 were ovariectomized on D2, implanted with an empty or E2 capsule, given 1 ml saline or PFF at 12.00 and 24.00 h, and bled 24 h following ovariectomy (OVX). Between D2 and proestrus plasma E2 levels increased, and there was no change in any parameter of pulsatile LH release. However, OVX on D2 reduced plasma E2 levels and increased mean blood LH levels above proestrous values due to increases in LH pulse amplitude and frequency. Restoration of physiological proestrous levels of E2 reduced the increase in mean blood LH levels, by lowering pulse frequency to proestrous values and by greatly reducing pulse amplitude. However, LH pulse amplitude and mean blood LH levels were still higher than values on proestrus. PFF alone produced no alteration in any parameter of pulsatile LH release compared with saline-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1981

Catecholamine turnover rates in discrete hypothalamic areas and associated changes in median eminence luteinizing hormone-releasing hormone and serum gonadotropins on proestrus and diestrous day 1.

We have correlated catecholamine [CA; i.e. norepinephrine (NE), dopamine (DA), and epinephrine (E)] turnover rates in discrete hypothalamic nuclei and in the median eminence (ME), with concentration changes in ME LHRH and serum LH, FSH, PRL, estradiol, and progesterone levels at various times during proestrus and diestrous day 1 in 4-day cyclic rats. CA concentrations were measured with a radioenzymatic assay at 0, 60, and 120 min after ip injection of 400 mg/kg alpha-methyl-p-tyrosine, and rate constants and turnover rates were calculated. In a separate assay NE, DA, and E were separated by two-dimensional thin layer chromatography, and concentrations and turnover rates of CAs were calculated. The microdissected hypothalamic nuclei examined for NE turnover rates included the medial preoptic nucleus (MPN), suprachiasmatic nucleus (SCN), arcuate nucleus (AN), and ME. DA turnover rates also were measured in the MPN, ME, and AN. ME LHRH and serum hormone concentrations were measured by RIA. Between 0900--1200 h, proestrous serum estradiol was elevated, but other serum hormones were basal, and CA turnover rates in the brain were low. However, ME LHRH concentrations increased significantly between 0900--1200 h on proestrus. Between 1200--1500 h, serum LH, FSH, PRL, and progesterone levels increased and ME LHRH levels declined significantly; during this time interval (1200--1400 h), a significant rise in ME NE and DA turnover rates occurred. Between 1500--1700 h on proestrus, while serum gonadotropins were still rising toward peak concentrations, increased ME NE turnover rates were maintained, but increased NE turnover rates also were evident in MPN, SCN, and AN. During this same time interval (1500--1700 h), a marked decline in ME and AN DA turnover rates occurred, although such rates remained unchanged within the MPN. There were no corresponding changes in MPN E turnover rates at any of the time intervals studied. The increased turnover rates of ME NE coupled with the concomitant decline in ME LHRH levels and the rise in plasma LH and FSH levels suggest that increased NE release may be important in initiating preovulatory LH and FSH surges. These changes in brain neurotransmitters and serum hormones are not the result of a diurnal rhythm, since corresponding changes in CA turnover rates or serum gonadotropins did not occur between 0900--1100 h and 1500--1700 h diestrous day 1.

Animals↗

PubMed1988

Role of oxytocin on prolactin secretion during proestrus and in different physiological or pharmacological paradigms.

The present study was designed to evaluate the possible physiological role of oxytocin (OXY) on PRL release by examining the effect of administration of potent pharmacological antagonists of OXY on the stimulation of PRL secretion observed in vitro from anterior pituitary (AP) cells in response to OXY administration or in a number of in vivo paradigms. OXY caused a dose-related increase in PRL release from dispersed AP cells and short term AP cell cultures which was blocked by administration of the OXY antagonists [1-deaminopenicillamine, 2-O-methyltyrosine, 8-ornithine]vasotocin (dPOMeOVT) or [1-(beta-mercapto-beta,beta-cyclopentamethylene propanoic acid)2-O-methyltyrosine, 8-ornithine]vasotocin (MPOMeOVT), respectively. The antagonists were given in vivo in a dose that completely blocked suckling-induced milk let-down for up to 90 min. Injection of the antagonists did not alter the 5-hydroxytryptophan-induced increase in plasma PRL or the increase associated with acute ether stress or acute suckling stimuli, suggesting that OXY is not a major component involved in the neuroendocrine mechanisms responsible for those particular increases. On the other hand, iv administration of dPOMeOVT or MPOMeOVT prevented the increase in plasma PRL normally observed on the afternoon of proestrus in the cycling female rat. The characteristic surge of LH was also blocked by high doses of these antagonists. These data demonstrate that PRL secretion undergoes a differential regulation, in that OXY appears to play a major role in regulating the increase in plasma PRL observed on the afternoon of proestrus, but apparently provides little, if any, contribution toward the neuroendocrine regulation of the increases in PRL associated with 5-hydroxytryptophan administration, acute ether stress stimulus, or acute suckling stimulus. The data also suggest that OXY receptors located in the AP that are involved in the OXY-induced increase in PRL release may be similar to those OXY receptors located in mammary and uterine tissue, since specific biological effects of OXY in those tissues are effectively blocked by the OXY antagonists dPOMeOVT and MPOMeOVT. A possible role of OXY neurons in the neural mechanisms triggering the LH surge during proestrus is also suggested.

Animals↗

PubMed1991

Regulation of ovarian steroid biosynthesis by estrogen during proestrus in the rat.

Studies were performed to test the hypothesis that the rapid decline in estradiol (E2) levels on proestrus before ovulation was due to a reduction in androgen substrate for aromatase, and that this decline in androgen was regulated by an estrogen receptor-mediated mechanism. Aromatase activity, concentrations of E2, androstenedione (A), testosterone (T), and progesterone (P4) in follicular, corpora lutea, and ovarian homogenates as well as peripheral E2, A, P4, and LH were measured in cycling rats from 1400-2000 h on proestrus. These parameters were also recorded after the expected E2 surge in animals treated at 1900 h on diestrous day 2 with the antiestrogen keoxifene (20 mg/kg), with or without an ovulatory dose of PMSG at 1600 h on proestrus. In a second experiment, P-450-17 alpha-hydroxylase/C17,20-lyase (P-450(17 alpha] activity was measured in a group of control rats at 1500, 1700, and 1900 h. Aromatase activity remained unchanged, even though serum and ovarian E2 levels were reduced from peak values at 1500 h to basal values at 1800 h (P less than 0.01). Peripheral A as well as ovarian androgens (specifically follicular but not luteal) A and T were also reduced over this time period (P less than 0.01). Although total ovarian P4 remained unchanged, follicular levels rose from 1400-2000 h (P less than 0.01). These reductions in androgens and E2 levels coincided with a marked reduction in follicular P-450(17 alpha) activity. Treatment with keoxifene with or without PMSG prevented the fall in peripheral E2 and A and the increase in peripheral P4 seen in controls. Ovarian and follicular E2, A, and to a lesser extent T were also remained at values similar to those during the E2 surge. Follicular P4 was reduced by both treatments. Neither treatment had any effect on aromatase. These results indicate that the fall in peripheral and ovarian E2 levels before ovulation was due to a decline in aromatizable androgen, through an inhibition of follicular P-450(17 alpha) enzyme activity, which appears to be mediated by an estrogen receptor-regulated mechanism.

Analysis of Variance↗

PubMed1995

Reconstructions of populations of luteinizing hormone releasing hormone neurons in young and middle-aged rats reveal progressive increases in subgroups expressing Fos protein on proestrus and age-related deficits.

Fos expression has been used as a marker of activation of neuroendocrine cells including LHRH neurons. In this study, Fos protein was localized within LHRH neurons in young and middle-aged rats to trace the temporal and spatial pattern of LHRH neuronal activation associated with the preovulatory LH surge. Animals were killed during the late morning, afternoon, and evening of proestrus. Dual immunocytochemical protocols localized LHRH and LHRH/Fos neurons, and computer-assisted methods were used to reconstruct forebrain populations of single- and double-labeled LHRH neurons. Although a significant increase in the number of LHRH/Fos neurons was noted by evening in both age groups, a greater increase was observed in young (12% in morning, 28% in afternoon, and 62% by evening) compared with aging females (5% in morning, 10% in afternoon, and 40% by evening). Reconstructions of LHRH and LHRH/Fos neurons revealed time- and age-dependent differences in Fos expression within LHRH neurons. In young females, LHRH/Fos neurons were restricted to central regions of the population of LHRH neurons on the morning of proestrus. By evening, Fos expression was also observed in more peripheral and caudal LHRH neurons. In middle-aged females, Fos expression was restricted to ventral subgroups of LHRH neurons on the afternoon of proestrus. By evening, more LHRH neurons contained Fos protein, however, few were located in the dorsal aspect of the population. These data trace the progressive increase in activation of LHRH neurons during the preovulatory LH surge in young females and reveal deficits in this pattern of activation by middle age.

Aging↗

PubMed1990

Suppression of the proestrus prolactin surge in the rat estrous cycle by urethane anesthesia.

Urethane-anesthetized male rats have been used for the analysis of prolactin (PRL)-releasing substances on PRL secretion. However, there are only a few reports investigating the effect of urethane anesthesia on PRL secretion in female rats. In this study, we intended to examine the effects of urethane anesthesia on PRL secretion during proestrus in the rat. Proestrus PRL surge was completely blocked when urethane was administered to rats prior to the critical period of proestrus both at doses of 1.0 g/kg and 1.5 g/kg. Additionally, urethane, at a dose of 1.5 g/kg, was also effective in blocking spontaneous ovulation. An experiment examining pituitary PRL concentration at 1800 h confirmed that urethane (1.0 g/kg) anesthesia prevents the PRL surge from the pituitary. Similarly, urethane anesthesia blocked the LH surge from the pituitary, but LH levels in the urethane-treated group were higher than those in the pentobarbital-treated group.

Anesthesia↗

PubMedDate not supplied

MyD88 and Src are differentially regulated in Kupffer cells of males and proestrus females following hypoxia.

Hypoxia produces sex dimorphic immune responses in males and proestrus females. Because Kupffer cells are the major source of proinflammatory cytokines, studies were conducted to discern IL-6 production in mouse Kupffer cells following hypoxia. Hypoxia enhances TLR4 expression in Kupffer cells irrespective of sex. However, MyD88 and Src expression in Kupffer cells decreased significantly after hypoxia in proestrus females, whereas Src protein expression and phosphorylation increased in males in concurrence with differences in IL-6 production. 17beta-estradiol administration elevated MyD88 and Src expression in males to levels in normoxic proestrus females. Administration of Src inhibitor in hypoxic males prevented increased IL-6 production. Thus, differential regulation of MyD88 and Src in males and females plays an important role in sex-specific immune response following hypoxia.

Animals↗

PubMed1985

Effect of cycloheximide [correction of cyclohexamide] injected at proestrus on ovarian protein synthesis, peptide and steroid hormone levels, and ovulation in the hamster.

Injecting 2 or 4 mg of cycloheximide (cyclo) at the onset of the proestrous release of gonadotropins prolongs the estrogen (E2) surge, diminishes progesterone (P4) secretion, and prevents ovulation by 0900 h of the next morning (Saidapur and Greenwald, 1981). The present study was designed to determine the effects of 0, 2, 4, or 8 mg cyclo injected at 1400 h proestrus (Day 4) on ovarian protein synthesis and other parameters. Ovulation was delayed until 1400 h estrus by 2 mg cyclo or prevented by 8 mg, and the latter treatment resulted in the death of all animals by 48 h. After 4 mg cyclo, ovulation was delayed in some animals, but the most characteristic feature was the development of large cystic follicles that ultimately transformed into corpora hemorrhagica. All animals lived after the injection of 4 mg cyclo. Ovaries collected 2, 8, 16, or 24 h after treatment were incubated with [3H]leucine for 1 h to assess the effects of cyclo on protein synthesis. Injection of phenobarbital at 1300 h proestrus, which blocks follicle-stimulating hormone (FSH) and luteinizing hormone (LH) surges, reduced ovarian protein synthesis at 1600 h to 61% of the control value. The incorporation of [3H]leucine was reduced to 75%, 37%, and 35% of the 1600-h control value by 2, 4, and 8 mg cyclo, respectively, but without affecting surge levels of FSH and LH. However, by 0600 h estrus, protein synthesis was increased significantly in all the cyclo-treated groups, which provides insight into the half-life of the compound (approximately equal to 8 h for 2-4 mg cyclo). At 1600 and 2200 h proestrus cyclo resulted in serum FSH and LH levels similar to controls, but increased serum prolactin and prolonged E2 levels at Day 4 of 2200 h and decreased serum P4 at both times. The second surge in FSH, which is in progress by 0600 h estrus, was abolished by 4 or 8 mg cyclo but not by the 2-mg dose. This is the first time for any species that ovarian protein synthesis has been measured in the proestrous normal or cyclo-treated animal. We conclude for the hamster that 4 mg cyclo is the optimal dose for blocking ovarian protein synthesis and ovulation and inducing formation of cystic follicles.

Animals↗