The effects of paradoxical sleep deprivation on estrous cycles of the female rats

The present purpose was to examine how sleep deprivation affects the estrous cycle of the female rat. Paradoxical sleep-deprived (PSD) adult female Wistar rats were compared to home-cage control (CTRL) on their estrous cyclicity. Forty-four PSD and forty-four CTRL female rats were distributed into 4 subgroups of 11 animals each according to the phase of estrous cycle and were subjected to sleep deprivation for 96 h by the multiple platform technique. After PSD period, vaginal estrous cycles were taken for an additional 9 days. Animals that were submitted to PSD in diestrus phase (PSD-diestrus) had their estrous cycles disrupted during the recovery period by showing a constant diestrus during the first week. As for hormone alterations, progesterone concentrations were statistically higher in PSD-diestrus compared to respective phase control and to PSD-proestrus and PSD-estrus rats while CTRL-metestrus had higher levels than CTRL-proestrus and estrus groups. Testosterone was significantly decreased in PSD-estrus in relation to PSD-proestrus and PSD-diestrus groups and was lower in CTRL-diestrus rats than in home-cage rats in proestrus. In addition, PSD-diestrus phase exhibited higher concentrations of corticosterone and lower estrogen than the respective control rats. These data indicate that PSD may modulate the ovarian hormone release through alterations in hormonal-neurochemical mechanisms.     

Exercise pressor reflex function in female rats fluctuates with the estrous cycle

In women, sympathoexcitation during static handgrip exercise is reduced during the follicular phase of the ovarian cycle compared with the menstrual phase. Previous animal studies have demonstrated that estrogen modulates the exercise pressor reflex, a sympathoexcitatory mechanism originating in contracting skeletal muscle. The present study was conducted in female rats to determine whether skeletal muscle contraction-evoked reflex sympathoexcitation fluctuates with the estrous cycle. The estrous cycle was judged by vaginal smear. Plasma concentrations of estrogen were significantly (P < 0.05) higher in rats during the proestrus phase of the estrus cycle than those during the diestrus phase. In decerebrate rats, either electrically induced 30-s continuous static contraction of the hindlimb muscle or 30-s passive stretch of Achilles tendon (a maneuver that selectively stimulates mechanically sensitive muscle afferents) evoked less renal sympathoexcitatory and pressor responses in the proestrus animals than in the diestrus animals. Renal sympathoexcitatory response to 1-min intermittent (1- to 4-s stimulation to relaxation) bouts of static contraction was also significantly less in the proestrus rats than that in the diestrus rats. In ovariectomized female rats, 17β-estradiol applied into a well covering the dorsal surface of the lumbar spinal cord significantly reduced skeletal muscle contraction-evoked responses. These observations demonstrate that the exercise pressor reflex function and its mechanical component fluctuate with the estrous cycle in rats. Estrogen may cause these fluctuations through its attenuating effects on the spinal component of the reflex arc.     

Orienting behavior of female white rats in estrus cycle and its dependence on handling

Characteristics of orienting behavior of intact and handled female white rats were studied in the "open field" test. Experimental group of animals were formed according to stages of estrous cycle: (1) diestrus, (2) proestrus, (3) estrus, and (4) metestrus. The stage of the cycle was determined by vaginal smears. Over the period of 10 days rats were handled daily for 5 minutes. No behavioral changes over the course of estrous cycle were found in intact rats. Handling revealed some behavioral features related to the levels of steroid hormones in reproductive cycle. Most prominent changes in orienting behavior were observed at transition from estrous to metestrous. At the stage of estrous motor activity was maximal and grooming was minimal. The maximal contrast in the structure of orienting behavior was observed between estrous and diestrous stages.     

Effects of thymulin and GnRH on the release of gonadotropins by in vitro pituitary cells obtained from rats in each day of estrous cycle

The effects of thymulin and GnRH on FSH and LH release were studied in suspension cultures of anterior pituitary cells from female adult rats sacrificed on each day of the estrous cycle. The spontaneous release of gonadotropins by pituitaries, as well as their response to GnRH or thymulin addition, fluctuated during the estrous cycle. Adding thymulin to pituitary cells from rats in diestrus 1 increased the concentration of FSH; while in cells from rats in estrus, FSH level decreased. Thymulin had a stimulatory effect on the basal concentration of LH during most days of the estrous cycle. Adding GnRH increased FSH release in cells from rats in diestrus 1, diestrus 2, or proestrus, and resulted in higher LH levels in cells obtained from rats in all days of the estrous cycle. Compared to the GnRH treatment, the simultaneous addition of thymulin and GnRH to cells from rats in diestrus 1, diestrus 2, or proestrus resulted in lower FSH concentrations. Similar results were observed in the LH release by cells from rats in diestrus 1, while in cells from rats in proestrus or estrus, LH concentrations increased. A directly proportional relation between progesterone serum levels and the effects of thymulin on FSH release was observed. These data suggest that thymulin plays a dual role in the release of gonadotropins, and that its effects depend on the hormonal status of the donor's pituitary.     

Variations in concentration of oxytocin and vasopressin in the paraventricular nucleus of the hypothalamus during the estrous cycle in rats

Oxytocin (OT) and arginine-8-vasopressin (AVP) were measured by radioimmunoassay in micropunched hypothalamic neurosecretory nuclei of estrous cycling female Sprague-Dawley rats. In the paraventricular nucleus (PVN): the concentration (pg/microgram protein) of OT was significantly higher in rats in diestrus than during proestrus, estrus, or metestrus, while the concentration during metestrus was significantly greater than in proestrus and estrus; the concentration of AVP was significantly lower in animals in estrus than during the other three stages; because the paraventricular OT levels dropped before proestrus, the AVP/OT ratio was significantly greater in animals in proestrus than in diestrus, metestrus, and estrus. In the supraoptic nucleus (SON) a similar trend was noted: the concentration of OT was highest during diestrus, and AVP was lowest during estrus, though neither was significantly different from other stages. Because the OT and AVP cycles in the SON were asynchronous, the ratio of AVP to OT was significantly higher in proestrus than in metestrus or diestrus and significantly greater in estrus than during diestrus. In contrast to these two areas, peptide concentrations did not vary significantly across the estrous cycle in other sites of nonapeptide synthesis, i.e. the anterior commissural nucleus (ACN) and the suprachiasmatic nuclei (SCN).     

Estrous Cycle Dependent Fluctuations of Regulatory Neuropeptides in the Lower Urinary Tract of Female Rats upon Colon-Bladder Cross-Sensitization

Co-morbidity of bladder, bowel, and non-specific pelvic pain symptoms is highly prevalent in women. Little evidence is present on modulation of pelvic pain syndromes by sex hormones, therefore, the objective of this study was to clarify the effects of hormonal fluctuations within the estrous cycle on regulatory neuropeptides in female rats using a model of neurogenic bladder dysfunction. The estrous cycle in female rats (Sprague-Dawley, 230–250 g) was assessed by vaginal smears and weight of uterine horns. Neurogenic bladder dysfunction was induced by a single inflammatory insult to the distal colon. Protein expression of calcitonin gene related peptide (CGRP), substance P (SP), nerve growth factor (NGF), and brain derived neurotrophic factor (BDNF) in the pelvic organs, sensory ganglia and lumbosacral spinal cord was compared in rats in proestrus (high estrogen) vs diestrus (low estrogen). Under normal physiological conditions, concentration of SP and CGRP was similar in the distal colon and urinary bladder during all phases of the estrous cycle, however, acute colitis induced a significant up-regulation of CGRP content in the colon (by 63%) and urinary bladder (by 54%, p≤0.05 to control) of rats in proestrus. These changes were accompanied by a significant diminution of CGRP content in L6-S2 DRG after colonic treatment, likely associated with its release in the periphery. In rats with high estrogen at the time of testing (proestrus), experimental colitis caused a significant up-regulation of BDNF colonic content from 26.1±8.5 pg/ml to 83.4±32.5 pg/ml (N = 7, p≤0.05 to control) and also induced similar effects on BDNF in the urinary bladder which was also up-regulated by 5-fold in rats in proestrus (p≤0.05 to respective control). Our results demonstrate estrous cycle dependent fluctuations of regulatory neuropeptides in the lower urinary tract upon colon-bladder cross-sensitization, which may contribute to pain fluctuations in female patients with neurogenic bladder pain.     

Effects of pregnancy and female sex steroid hormones on calcitonin gene-related peptide content of mesenteric artery in rats

Calcitonin gene-related peptide (CGRP) levels in plasma and the dorsal root ganglia (DRG) are increased during pregnancy and in ovariectomized rats injected with ovarian hormones. Vasodilatory responses to CGRP are also increased in these animals. In the present study, we hypothesized that pregnancy and ovarian hormones elevate the contents of CGRP in perivascular nerves. We assessed CGRP-dependent mesenteric vascular relaxation induced by electrical field stimulation (EFS) and arterial content of CGRP. Because the mesenteric artery represents resistance vessels, segments of mesenteric arteries collected from female rats at different stages of the estrous cycle, pregnancy, or postpartum and from male rats were used in this study. The EFS-induced relaxation in the presence and absence of CGRP(8-37), an antagonist of CGRP, was used to measure CGRP-dependent relaxation, and radioimmunoassay (RIA) of tissue homogenates was used to assess changes in CGRP content in mesenteric branch arteries. The results show that CGRP-dependent, EFS-induced relaxation response was lower in female rats at diestrus and proestrus than in male rats, and no statistically significant differences were observed between Gestational Day 20 and Postpartum Day 2. The RIA revealed significantly lower mesenteric artery CGRP levels in female rats at proestrus, gestation, and postpartum than in female rats at diestrus or in male rats. We conclude that no correlation exists between CGRP-dependent, EFS-induced relaxation and CGRP content in the mesenteric arteries of these animal groups. Because both CGRP levels in DRG and serum are reported to be elevated, the reduced CGRP content in the vasculature during pregnancy and proestrus implicate enhanced basal release of CGRP at the nerve terminal in these animals.     

Effect of plastoquinone derivative 10-(6′-Plastoquinonyl) decyltriphenylphosphonium (SkQ1) on estrous cycle and 17β-estradiol level in rats

Administration of the plastoquinone derivative 10-(6??-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to female Wistar rats with regular estrous cycle once a day for two weeks at doses of 25 nmol/kg (but not 250 nmol/kg) leads to increase in proestrus duration by reducing the phase of diestrus and metestrus. Neither dose caused significant changes in serum 17??-estradiol level for any stage of the cycle. However, relative elongation of the proestrus stage leads to an increase in average per cycle estradiol levels by 20%.     

Oxytocin secretion induced by osmotic stimulation in rats during the estrous cycle and after ovariectomy and hormone replacement therapy

Hyperosmolality is a potent stimulus for the secretion of oxytocin. Oxytocinergic neurons are modulated by estrogen and oxytocin secretion in rats varies according to the phase of the estrous cycle, with higher activity during proestrus. We investigated the oxytocin secretion induced by an osmotic stimulus (0.5 M NaCl) in female rats. Plasma oxytocin and the oxytocin contents in the neurohypophysis and the paraventricular and supraoptic nuclei were determined during the morning (8-9 h) and afternoon (17-18 h) of the estrous cycle and after ovariectomy followed or not by hormone replacement. Plasma oxytocin peaked in control animals during proestrus. Oxytocin content decreased in the paraventricular and supraoptic nuclei during proestrus and estrus compared to diestrus and increased in the neurohypophysis during proestrus morning. No significant difference was observed in the oxytocin content of the neurohypophysis, nuclei or plasma between ovariectomized animals and ovariectomized animals treated with estrogen or estrogen plus progesterone. Therefore, any ovarian factor other than estrogen or progesterone seems to play a direct or indirect role in the increase in oxytocin secretion. The osmotic stimulus caused an increase in plasma oxytocin throughout the estrous cycle. A reduction in oxytocin content during diestrus and an increase during proestrus were observed in the paraventricular nuclei. In ovariectomized animals, the treatment with estrogen potentiated the response of oxytocin to the osmotic stimulus, with the response being even stronger in the case of estrogen plus progesterone. In conclusion, the ovarian steroids estrogen plus progesterone could modulate the osmoreceptor mechanisms related to oxytocin secretion.     

Differences in prolyl-leucyl-glycinamide metabolism by hypothalamus,pituitary and cerebral cortex of male and female rats

l-Prolyl-l-leucyl-glycinamide is rapidly hydrolyzed by hypothalamic, hypophyseal and cortical homogenates from male or female rats. The peptidase activity is higher in the pituitary followed in decreasing order by the hypothalamus and the cerebral cortex. It is mostly localized in the supernatant fraction of a 100,000 g centrifugation and is inhibited by bacitracin.Tissues from female rats are half as active as those from male rats and show variations during the estrous cycle, with very low PLG metabolism at diestrus 1 in pituitary and hypothalamus. In contrast, the cerebral cortex at proestrus and estrus has significant lower hydrolyzing activity than at diestrus. No change of the peptidase activity is observed in tissues from ovariectomized animals after treatment with estrogen or progesterone.The results obtained suggest the existence of a correlation between peptidasic activity and melanotropin secretion.     

Sex and estrous cycle-dependent differences in glial fibrillary acidic protein immunoreactivity in the adult rat hippocampus

Sex differences in the morphology and function of the hippocampus have been reported in several species, but it is unknown whether a sexual dimorphism exists in glial fibrillary acidic protein (GFAP) expression in the rat hippocampus. We analyzed GFAP immunoreactivity in the hippocampus of intact adult male rats as well as in females during diestrus and proestrus phases of the estrous cycle. We found that in CA1, CA3, and dentate gyrus, GFAP immunoreactivity was higher in proestrus females as compared with males and diestrus females. In CA1, a similar GFAP immunoreactivity was found in males and in diestrus females, but in dentate gyrus, males presented the lowest GFAP content. Interestingly, differences in astrocyte morphology were also found. Rounded cells with numerous and short processes were mainly observed in the hippocampus during proestrus whereas cells with stellate shape with few and long processes were present in the hippocampus of males and diestrus females. The marked sex and estrous cycle-dependent differences in GFAP immunoreactivity density and in astrocyte number and morphology found in the rat hippocampus, suggest the involvement of sex steroid hormones in the sexually dimorphic functions of the hippocampus, and in the change in its activity during the estrous cycle.     

Differential impact of cocaine on meal patterns in female and male rats

Female rats, relative to males, exhibit greater behavioral activation to cocaine and other psychostimulants, but the effect of sex and the estrous cycle in modulating the hypophagic action of cocaine has not been evaluated. Meal patterns were recorded in automated food hoppers during the first 3 h of the dark phase in adult female and male rats after administration of ascending cocaine doses (0, 7.5, and 15 mg/kg cocaine, i.p.) on successive trials. Cocaine produced a greater suppression of feeding as well as a reduction in meal number over a 3 h test period in female rats during estrus, relative to that noted during diestrus. In contrast, during the 180 min test period, male rats showed minimal hypophagic responses to 7.5 or 15 mg/kg cocaine. These results extend the range of behavioral perturbations induced by cocaine that are modulated by sex and by the estrous cycle and are consistent with the notion that estradiol may modulate the neurochemical actions of cocaine.     

Neonatal Immune Challenge with Lipopolysaccharide Triggers Long-lasting Sex- and Age-related Behavioral and Immune/Neurotrophic Alterations in Mice: Relevance to Autism Spectrum Disorders

Early-life challenges, particularly infections and stress, are related to neuropsychiatric disorders such as autism and schizophrenia. Here, we conducted a wide range of behavioral tests in periadolescent (postnatal day (PN) 35) and adult (PN70) Swiss mice neonatally challenged with LPS on PN5 and -7, to unveil behavioral alterations triggered by LPS exposure. Immune and neurotrophic (brain-derived neurotrophic factor—BDNF) alterations were determined in the prefrontal cortex (PFC), hippocampus (HC), and hypothalamus (HT). Since the incidence and clinical manifestations of neurodevelopmental disorders present significant sex-related differences, we sought to distinctly evaluate male and female mice. While on PN35, LPS-challenged male mice presented depressive, anxiety-like, repetitive behavior, and working memory deficits; on PN70, only depressive- and anxiety-like behaviors were observed. Conversely, females presented prepulse inhibition (PPI) deficits in both ages studied. Behavioral changes in periadolescence and adulthood were accompanied, in both sexes, by increased levels of interleukin (IL-4) (PFC, HC, and HT) and decreased levels of IL-6 (PFC, HC, and HT). BDNF levels increased in both sexes on PN70. LPS-challenged male mice presented, in both ages evaluated, increased HC myeloperoxidase activity (MPO); while when adult increased levels of interferon gamma (IFNγ), nitrite and decreased parvalbumin were observed. Alterations in innate immunity and parvalbumin were the main LPS-induced remarks between males and females in our study. We concluded that neonatal LPS challenge triggers sex-specific behavioral and neurochemical alterations that resemble autism spectrum disorder, constituting in a relevant model for the mechanistic investigation of sex bias associated with the development of this disorder.     

QRFP in female rats: effects on high fat food intake and hypothalamic gene expression across the estrous cycle

Pyroglutamylated arginine-phenylalanineamide peptide (QRFP) is a neuropeptide involved in feeding behavior. Central administration of QRFP selectively increases the intake of a high fat diet in male rats. QRFP administration also stimulates the hypothalamic-pituitary-gonadal axis via gonadotrophin-releasing hormone in male and female rats. Prepro-QRFP mRNA is expressed in localized regions of the mediobasal hypothalamus which are abundant in neurotransmitters, neuropeptides and receptor systems important for food intake regulation and reproductive behaviors. The current experiments were conducted to investigate the effects of centrally administered QRFP-26 on the intake of a high fat diet (HFD, 60% kcal from fat) in female rats and to investigate alterations in hypothalamic prepro-QRFP and its receptors, GPR130a and GPR103b, mRNA levels over the estrous cycle. In Experiment 1, female rats were administered QRFP-26 (intracerebroventricular; 0.3 nmol, 0.5 nmol, 1.0 nmol) in rats consuming either a HFD or a low fat diet. All doses of QRFP-26 selectively increased the intake of the HFD in female rats. These data suggest that QRFP-26 regulates the intake of energy dense foods in female rats, which is similar to previous findings in male rats. In Experiment 2, hypothalamic levels of prepro-QRFP mRNA and its receptors were assessed during diestrus, proestrus, or estrus. The level of prepro-QRFP mRNA in the ventromedial/arcuate nucleus (VMH/ARC) of the hypothalamus was increased during proestrus, which suggests that endogenous estrogen levels regulate QRFP expression in the VMH/ARC. These data suggest that QRFP may play a role in coordinating feeding behaviors with reproductive function when energy demand is increased.     

Atrial supersensitivity to noradrenaline in stressed female rats

Stress can change the responses to catecholamines in many tissues. The aim of this study was to investigate the influence of the estrous cycle on the sensitivity of right atria to noradrenaline in female rats subjected to acute swimming stress. Female Wistar rats in proestrus, estrus, metestrus or diestrus were submitted to a 50 min-swimming session. Immediately after the exercise, the rats were killed and their right atria were mounted for isometric recording of the spontaneous beating rate. Concentration-effect curves to noradrenaline were obtained before and after the inhibition of neuronal uptake with phenoxybenzamine (10 microM) and of extraneuronal uptake with estradiol (5 microM). Acute swimming stress did not change the right atrial sensitivity to noradrenaline in rats in estrus, metestrus and diestrus. However, swimming stress produced supersensitivity to noradrenaline in proestrus (pD(2) control: 7.14 +/- 0.03 vs. pD(2) swimming: 7.55 +/- 0.04; p<0.05). This supersensitivity was still observed after uptake inhibition. When catecholamine uptake was inhibited, the concentration-effect curve to noradrenaline was shifted to the left 2.5-fold in the proestrus control group and 1.7-fold in the proestrus stress group (p<0.05). In conclusion, the estrous cycle influenced the acute stress-induced atrial supersensitivity to noradrenaline.     

Prolactin receptors in the rat mammary gland. Change during the estrous cycle

Ovine prolactin (o-PRL) binding to mammary gland membranes was studied during the estrous cycle in the rat. Groups of rats were decapitated throughout the 4-day estrous cycle at 10 h00 on the days of diestrus I, diestrus II and estrus and at 10 h00, 12 h00, 16 h00 during the day of proestrus. Daily vaginal smears were taken to determine the stage of the estrous cycle which was also controlled by PRL and LH serum levels. Prolactin receptors were quantified in the 100 000 g pellet. For one Scatchard analysis, mammary gland membranes from 5 animals were pooled. Results given are the mean of 4 or 5 pools. Results obtained showed that the apparent affinity constant (KA) remained unchanged during the days of diestrus II and at all the times studied of proestrus and showed a slight but significant decrease on the days of estrus and diestrus I (or metestrus). The binding capacity did not vary from the day of diestrus II to the proestrus 16h00 (11.3 +/- 2.8 fmoles/mg protein) but sharply increased on the day of estrus (190.4 +/- 35.9 fmoles/mg protein). Binding capacity remained elevated on the day of diestrus I. This increase of PRL receptors on the day of estrous would appear to be an important step in preparing mammary gland for pregnancy and lactation.     

The beta1-adrenoceptor site activated by CGP12177 varies in behavior according to the estrous cycle phase and stress

The aim of this work was to assess whether stress and estrous cycle phases affected the beta1-adrenoceptor (beta1-AR) site activated by CGP12177 in the right atria of rats. The chronotropic response to CGP12177 in the absence or presence of antagonists was determined in atria from rats submitted to one daily foot-shock session for 3 consecutive days. Blood was collected for hormonal assays. The pD2 for CGP12177 in atria from females was lower than in atria from males and was unaltered by stress or the estrous cycle. Propranolol (200 nM) or CGP20712A (3 microM) shifted the concentration-response curves to CGP12177 to the right in control and stressed estrus or control diestrus rats. Atria from stressed diestrus rats were resistant to blockade by propranolol or CGP20712A, indicating that the effect of beta-adrenoceptor antagonists on the response to CGP12177 is influenced by estrous cycle phases. The stress-induced increase in serum corticosterone levels was independent of the estrous cycle or gender, but the estradiol/progesterone ratio was affected differently in the two groups of female rats. In the diestrus group, serum estradiol levels decreased after the first foot-shock session and remained low until the day of sacrifice, whereas in the estrus group the serum levels of estradiol did not decrease after stress and peaked on the second day, which corresponded to proestrus. These data do not indicate whether there is a direct or indirect effect of stress hormones and (or) sex steroids on cardiac beta1-AR sensitivity. However, they do show that the classic and low-affinity binding sites of the beta1-AR are independently regulated and that the beta1-AR atypical site affinity for antagonists depends on the estrous cycle.     

Amygdala activation by corticosterone alters visceral and somatic pain in cycling female rats

Irritable bowel syndrome (IBS) is often seen in women, and symptom severity is known to vary over the menstrual cycle. In addition, activation of the hypothalamic-pituitary-adrenal (HPA) axis enhances symptomology and patients with IBS have increased activation of the amygdala, a brain region known to facilitate HPA output. However, little is known about the effects of amygdala activation during different stages of the menstrual cycle. We therefore investigated the effects of amygdala activation on somatic and visceral pain perception over the rat estrous cycle. Female Wistar rats were implanted with either corticosterone (Cort) or cholesterol as a control onto the dorsal margin of the central amygdala. Visceral sensitivity was quantified by recording the visceromotor response (VMR) to colorectal distension (CRD) and somatic sensitivity was assessed via the Von Frey test. In cholesterol controls, both visceral and somatic sensitivity varied over the estrous cycle. Rats in proestrus/estrus responded to CRD with an increased VMR compared with rats in metestrus/diestrus. Somatic sensitivity followed a similar pattern with enhanced sensitivity during proestrus/estrus compared with metestrus/diestrus. Elevated amygdala Cort induced visceral hypersensitivity during metestrus/diestrus but had no effect during proestrus/estrus. In contrast, elevated amygdala Cort increased somatic sensitivity during both metestrus/diestrus and proestrus/estrous. These results suggests that amygdala activation by Cort eliminates spontaneously occurring differences in visceral and somatic pain perception, which could explain the lowered pain thresholds and higher incidence of somatic pain observed in women with IBS.     

Photoaffinity labeling of pituitary gonadotropin releasing hormone receptors during the rat estrous cycle

A bioactive photoaffinity derivative of gonadotropin releasing hormone was used to identify pituitary gonadotropin releasing hormone receptors at various stages of the rat estrous cycle. Sodium dodecyl sulfate polyacrylamide gel electrophoresis resulted in the identification of a single specific component with an apparent molecular weight of 60,000 daltons throughout the estrous cycle. The amount of radioactivity incorporated into the 60K dalton band in diestrus and proestrus female rats increased 2.5-fold to that of metestrus and estrus female rats. These findings provide additional evidence for the identification of pituitary gonadotropin releasing hormone receptors.     

The effect of the estrous cycle and estrogen on the release of immunoreactive alpha-melanocyte-stimulating hormone

Circulating levels and tissue content of alpha-MSH were measured on the morning of various days of the estrous cycle, and on the afternoon of proestrus in freely moving conscious rats. No surges of alpha-MSH were detected by RIA in the morning of various days of the cycle. The neurointermediate lobe content of alpha-MSH was slightly elevated on diestrus 1 as compared to the levels on diestrus 11 and proestrus but not to estrous levels. No changes in alpha-MSH content were detected in the anterior pituitary, the median eminence, mediobasal hypothalamus and the preoptic area at various stages of the estrous cycle. Plasma alpha-MSH levels were slightly elevated at 1500 hr of proestrus which was followed three hours later by a decline. This profile of plasma alpha-MSH on the afternoon of proestrus was reproduced by the SC administration of estradiol benzoate to long-term ovariectomized rats. These data suggest that, contrary to the results obtained by bioassay of alpha-MSH no surges of alpha-MSH occur on any day of the cycle, although a slight elevation on the afternoon of proestrus was detected. The altered pattern of release of this peptide on the afternoon of proestrus may be induced by estrogen.