Role Of Ovarian Steroids Research Articles

Estrogen Influences on Neuromuscular Function in Postmenopausal Women

Exposure to ovarian sex steroids during different life phases has long-term effects on women's health and wellbeing. Menopause is characterized by rapid decline in ovarian sex steroids already during mid-life, between the ages of 46 and 52. Due to the menopause-related hormonal changes, women in most western countries live more than one-third of their lives in postmenopausal status. The role of ovarian steroids on neuromuscular function in middle-aged and older women has been investigated since the 1980s with increasing volume of research during the last decades. This review considers how different components of the neuromuscular system may be influenced by estrogens and so affects neuromuscular function in postmenopausal women. The main focus is on muscle strength and power, which are closely associated with mobility and functional capacity among older populations. In the end of the review, we summarize recent findings on the underlying biological mechanisms in skeletal muscle that could explain the association between hormone replacement therapy and neuromuscular function among postmenopausal women.

Opioid modulation of prolactin secretion induced by stress during late pregnancy. Role of ovarian steroids

BackgroundThe opioid system modulates prolactin release during late pregnancy. Its role and the participation of ovarian hormones in this modulation are explored in ether stress-induced prolactin release. Methods/ResultsEstrous, 3-day and 19-day pregnant rats were used. We administered the antagonist mifepristone (Mp) and tamoxifen to evaluate progesterone and estradiol action in naloxone (NAL, opioid antagonist) or saline treated rats. Ether stress had no effect on serum prolactin levels in controls but increased prolactin release in NAL-treated rats. Prolactin response to stress in NAL-treated rats was blocked by l-DOPA administration. Mp treatment on day 18 of pregnancy increased prolactin levels after stress without alterations by NAL. Tamoxifen on days 14 and 15 of pregnancy completely blocked Mp and NAL effects on prolactin release at late pregnancy. In contrast, stress significantly increased prolactin levels in estrous rats and pretreatment with NAL prevented this. On day 3 of pregnancy, at 6.00 p.m., stress and NAL treatment inhibited prolactin levels in saline-treated rat. No effect of stress or NAL administration was detected on day 3 of pregnancy at 9.00 a.m. icv administration of specific opioids antagonist, B-Funaltrexamine but not Nor-Binaltorphimine or Naltrindole, caused a significant increase in stress-induced prolactin release. ConclusionsOpioid system suppression of prolactin stress response during late pregnancy was observed only after progesterone withdrawal, involving a different opioid mechanism from its well-established stimulatory role. This mechanism acts through a mu opioid receptor and requires estrogen participation. The opioid system and progesterone may modulate stress-induced prolactin release, probably involving a putative prolactin-releasing factor.

Duodenumda Ovaryum Steroidlerinin Etkisinde Nitrik Oksidin Rolü

Summary The purpose of this study is to determine the distribution and expression of nNOS, eNOS and iNOS and to evaluate the role of ovarian steroids in NOS expressions in the duodenum tissues of rats. Rats in the control group (Ov group) were injected intramuscularly with sesame oil for 10 days, whereas rats in the first, second, and third experimental groups received intramuscular administration of progesterone (P group), 17β-estradiol (E2 group) and 17beta-estradiol and progesterone (E2 + P group), respectively. According to the results of an immunohistochemical evaluation, a severe nNOS expression was observed in both the crypts and nerve fibers of the duodenum in the Ov, P and E2 groups but decreased in the E2 + P group. It was determined that iNOS expression increased in the surface epithelial cells and crypts of P group while it only decreased in crypts of E2 group. There was severe eNOS expression in crypts in all treatment groups, while it only increased in the surface epithelial cells in the E2 group. The results of the current experiment suggest that the effect of ovarian steroids on duodenum absorbtion and microvascular protection can be mediated by crypt and epithelial nNOS, iNOS and eNOS expressions in rats. Besides the estradiol and progesterone administration together inhibit nNOS activitiy in the duodenum.

Hippocampal volume in postmenopausal cynomolgus macaques with behavioral depression.

Magnetic resonance imaging (MRI) studies report hippocampal (HC) volume reductions in depression. Despite observations of functional heterogeneity and ovarian steroid influence in the hippocampus, few studies report regional volume alterations or control for menstrual cycle phase. Using in vitro methods, we recently observed reduced anterior HC volume in antidepressant-naive, ovarian-intact, behaviorally depressed adult female monkeys. The purpose of this study was to confirm these findings in vivo and examine whether lack of ovarian steroids affects the relationship between depression and HC volume. MRI was used to measure whole, anterior, and posterior HC volumes in a matched sample of antidepressant-naive, surgically postmenopausal adult female cynomolgus macaques characterized for behavioral depression (six depressed, six nondepressed). High-resolution structural MRIs were acquired, and HC regions of interest were manually segmented. HC volumes were normalized to whole brain volumes before analysis. Similar to the previous in vitro study, HC volume measured in vivo was associated with depression. In contrast to the previous study of ovarian-intact female monkeys, whole, anterior, and posterior volumes of both the left and right hippocampi were significantly smaller in depressed compared with nondepressed surgically postmenopausal female monkeys. These findings confirm and extend previous observations of smaller HC volumes in behaviorally depressed female monkeys and suggest a possible role for ovarian steroids in HC protection in depression. Further studies of the potential modulating effects of ovarian function on the relationship between depression and HC volume are warranted.

Modulatory role of locus coeruleus and estradiol on the stress response of female rats

The activity of the hypothalamic-pituitary-adrenal axis is modulated by the norepinephrinergic system and, in females, also by the ovarian hormones. We investigated the role of ovarian steroids and the locus coeruleus (LC) on stress-induced corticosterone secretion in female rats. Ovariectomized rats without hormonal replacement (OVX) or treated with estradiol (OVE) or estradiol plus progesterone (OVEP) were subjected to jugular cannulation. Immediately after that, each hormonal treatment group was subjected to LC lesion or sham surgery or no brain surgery. After 24 h, blood samples of all 9 groups were collected before and after ether inhalation. Other four groups (OVX control, sham and lesioned, and OVE) were perfused for glucocorticoid receptor (GR) immunocytochemistry in hippocampal CA1 neurons and paraventricular nucleus (PVN). Estradiol replacement decreased while LC lesions increased stress-induced corticosterone secretion. The effect of LC lesion was potentiated with the removal of ovarian steroids. Since GR expression of lesioned animals decreased in the hippocampus, but not in PVN, we suggest that the effect of LC lesion on corticosterone secretion could be due to a reduction in the efficiency of the negative feedback system in the CA1 neurons. However, this mechanism is not involved in the estradiol modulation on corticosteroid secretion, as no change in GR expression was observed in estradiol-treated animals.

Increased Caloric Intake on a Fat‐Rich Diet: Role of Ovarian Steroids and Galanin in the Medial Preoptic and Paraventricular Nuclei and Anterior Pituitary of Female Rats

Previous studies in male rats have demonstrated that the orexigenic peptide galanin (GAL), in neurones of the anterior parvocellular region of the paraventricular nucleus (aPVN) projecting to the median eminence (ME), is stimulated by consumption of a high-fat diet and may have a role in the hyperphagia induced by fat. In addition to confirming this relationship in female rats and distinguishing the aPVN-ME from other hypothalamic areas, the present study identified two additional extra-hypothalamic sites where GAL is stimulated by dietary fat in females but not males. These sites were the medial preoptic nucleus (MPN), located immediately rostral to the aPVN, and the anterior pituitary (AP). The involvement of ovarian steroids, oestradiol (E(2)) and progesterone (PROG), in this phenomenon was suggested by an observed increase in circulating levels of these hormones and GAL in MPN and AP with fat consumption and an attenuation of this effect on GAL in ovariectomised (OVX) rats. Furthermore, in the same four areas affected by dietary fat, levels of GAL mRNA and peptide immunoreactivity were stimulated by E(2) and further by PROG replacement in E(2)-primed OVX rats and were higher in females compared to males. Because both GAL and PROG stimulate feeding, their increase on a fat-rich diet may have functional consequences in females, possibly contributing to the increased caloric intake induced by dietary fat. This is supported by the findings that PROG administration in E(2)-primed OVX rats reverses the inhibitory effect of E(2) on total caloric intake while increasing voluntary fat ingestion, and that female rats with higher GAL exhibit increased preference for fat compared to males. Thus, ovarian steroids may function together with GAL in a neurocircuit, involving the MPN, aPVN, ME and AP, which coordinate feeding behaviour with reproductive function to promote consumption of a fat-rich diet at times of increased energy demand.

Premenstrual Symptoms and Perimenopausal Depression

The role of ovarian steroids in both premenstrual dysphoria and perimenopausal depression has led to the suggestion that these conditions represent expressions of the same underlying disorder. Premenstrual mood symptoms were evaluated in women with perimenopause-related depression. Self-reports and daily symptom ratings during one menstrual cycle were examined in 70 depressed perimenopausal women attending a menopause clinic and 35 nondepressed perimenopausal women. Twenty-six percent of the depressed and 9% of the nondepressed women reported premenstrual symptoms. Thirty-one percent of the depressed and 20% of the nondepressed women met criteria for significant menses-related symptom cyclicity (at least a 30% increase in the average ratings of at least two of four measured negative mood symptoms in the premenstrual versus the postmenstrual week); 5 of these depressed women and none of the comparison subjects described premenstrual symptoms on self-reports. Finally, 21% of the depressed and 3% of the nondepressed women met criteria for premenstrual dysphoria (symptom cyclicity and at least moderate severity, with symptoms exceeding a minimum luteal symptom severity threshold of 2.5). A higher-than-expected rate of menses-related symptom cyclicity and premenstrual dysphoria was observed in perimenopausal depressed women. However, neither menses-related symptom cyclicity nor premenstrual dysphoria was an invariant accompaniment of perimenopausal depression. Additionally, the rate of premenstrual dysphoria was not predicted by initial self-reports.

Sex and estrous cycle differences in the behavioral effects of high-strength static magnetic fields: role of ovarian steroids

Advances in magnetic resonance imaging are driving the development of higher-resolution machines equipped with high-strength static magnetic fields (MFs). The behavioral effects of high-strength MFs are largely uncharacterized, although in male rats, exposure to 7 T or above induces locomotor circling and leads to a conditioned taste avoidance (CTA) if paired with a novel taste. Here, the effects of MFs on male and female rats were compared to determine whether there are sex differences in behavioral responses and whether these can be explained by ovarian steroid status. Rats were given 10-min access to a novel saccharin solution and then restrained within a 14-T magnet for 30 min. Locomotor activity after exposure was scored for circling and rearing. CTA extinction was measured with two-bottle preference tests. In experiment 1, males were compared with females across the estrous cycle after a single MF exposure. Females circled more and acquired a more persistent CTA than males; circling was highest on the day of estrus. In experiment 2, the effects of three MF exposures were compared among intact rats, ovariectomized females, and ovariectomized females with steroid replacement. Compared with intact rats, ovariectomy increased circling; estrogen replacement blocked the increase. Males acquired a stronger initial CTA but extinguished faster than intact or ovariectomized females. Thus the locomotor circling induced by MF exposure was increased in females and modulated by ovarian steroids across the estrous cycle and by hormone replacement. Furthermore, female rats acquired a more persistent CTA than male rats, which was not dependent on estrous phase or endogenous ovarian steroids.

Regulation by endogenous opioids of suckling-induced prolactin secretion in pregnant and lactating rats: role of ovarian steroids.

Evidence suggests that endogenous opioid peptides are implicated in the suckling-induced prolactin rise. We explored the role of the opioid system and the participation of ovarian hormones in the regulation of prolactin induced by the suckling stimulus at the end of pregnancy in rats with developed maternal behavior, and during lactation. Suckling for 24 h induced a significant increase in serum prolactin on day 19 of pregnancy, which was increased more than three times when naloxone (2 mg/kg s.c.) or mifepristone (2 mg/kg) was administered. The combination of naloxone and mifepristone did not increase serum prolactin more than either compound alone. Administration of tamoxifen (500 microg/kg orally) on days 14 and 15 of pregnancy completely abolished the effect of naloxone, indicating a role for estrogens in establishing this inhibitory role of opioids. To examine the participation of the opioid system during lactation, we used groups of rats on days 1, 3, 5, 12 and 19 postpartum either (i) isolated from the pups for 4 h, or (ii) isolated from the pups for 3.5 h and reunited with them and suckled for 30 min. Naloxone, given just before replacing the pups, prevented the increase in serum prolactin levels observed in the suckled group of rats but had no effect on the basal levels of the isolated rats. To examine whether the participation of the opioid system in the release of prolactin is dependent on the variation of progesterone levels, rats on day 20 of pregnancy were implanted with two cannulae containing progesterone (that blocked postpartum ovulation) or cholesterol, and cesarean surgery was performed on day 21. To maintain lactation, pups (1-3 days old) were replaced every 24 h, and 4 days after the cesarean eight pups were placed in the cage at 1800 h to maintain a strong suckling stimulus during the following 24 h. Naloxone administration significantly reduced serum prolactin levels in control (cholesterol) rats but progesterone implants prevented the inhibitory effect of naloxone and this effect was not modified by treatment with estrogen. These results indicate that the opioid system modulates suckling-induced prolactin secretion, passing from an inhibitory action before delivery to a stimulatory action during lactation. This regulatory shift seems to be dependent on the fall in progesterone concentration at the end of pregnancy and the subsequent increase after the postpartum ovulation and luteal phase.

Oxytocin receptor gene expression in rat uterus: regulation by ovarian steroids.

The present study was designed to investigate a possible role for ovarian steroids in the regulation of rat uterine oxytocin receptor (OTR) mRNA expression before labour. By using a competitive RT-PCR system, we have previously reported that parturition was associated with high levels of uterine OTR mRNA in all the animals examined. On the other hand, near term, some rats showed high OTR mRNA levels while others did not. We therefore examined the changes in OTR mRNA expression before and during prostaglandin F(2)(alpha) (PGF(2)(alpha))-induced parturition; a paradigm adopted to reduce the variation in the onset of parturition. Injection of PGF(2)(alpha) on day 18 of pregnancy significantly increased OTR mRNA expression in all the rats within 24 h of treatment, suggesting that the variation in OTR mRNA levels during spontaneous parturition may be due to the difference in the timing of the onset of parturition. The increase in OTR mRNA was significantly abolished by injection of the anti-oestrogen compound, tamoxifen. The stimulatory action of oestrogen on OTR mRNA expression was then examined in the presence or absence of ovarian factors. Pregnant rats were ovariectomized (OVX) or sham-operated on day 18 of pregnancy and either oestrogen or vehicle was administered 6 h after the surgical operation. Oestrogen increased OTR mRNA significantly in OVX rats 18 h after administration compared with sham-operated animals. Moreover, ovariectomy alone on day 18 of pregnancy increased OTR mRNA expression to a level which reached statistical significance 24 h after the operation. In addition, oestrogen treatment increased OTR mRNA levels in OVX virgin rats in which progesterone tubes were implanted for 1 week and removed 6 h before oestrogen injection. The stimulatory effect of oestrogen was not observed in rats in which the progesterone tubes were implanted for 1 week and not removed. These results suggest that the decline of progesterone is necessary for the expression of the stimulatory effects of oestrogen on uterine OTR mRNA.

Changes of circulating leptin levels during normal menstrual cycle: relationship to estradiol and progesterone.

A possible role of ovarian steroids on the modulation of leptin production has recently been suggested. To investigate the relationship between leptin and ovarian steroids during the normal menstrual cycle, twenty-three healthy, normal-weight women were enrolled in the study. Blood was collected into chilled EDTA tubes on cycle days (D) 3, 7, 10, preovulatory (D13-15), midluteal (D 21-23) and late luteal (D 25-27) phases. Plasma leptin, estradiol (E2), progesterone (P), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured by RIA. Leptin levels showed no significant changes throughout the follicular (D7 and D10), preovulatory (8.6 +/- 0.5 ng/mL), midluteal (8.9 +/- 0.6 ng/mL) and late luteal (7.7 +/- 0.4 ng/mL) phases, as compared with those of D3 (7.4 +/- 0.5 ng/mL) level. There was no positive correlation between leptin and E2 levels in D 3 and D 7 (r = 0.14, P > 0.05) or in D 10 and preovulatory day (r = 0.25, P > 0.05). Also, no positive correlation between leptin and E2 (r = 0.12, P > 0.05) or leptin and P (r = 0.17, P > 0.05) levels were observed in the mid- and late luteal phases. These data clearly indicate that physiological alterations of circulating E2 and P concentrations have no significant influence on the leptin changes during normal menstrual cycle.

Changes in NADPH-d staining in the paraventricular and supraoptic nuclei during pregnancy and lactation in rats: role of ovarian steroids and oxytocin.

Staining for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a histochemical marker for nitric oxide synthase (NOS), is increased in the supraoptic (SON) and paraventricular (PVN) nuclei in late pregnant rats. To determine whether increases in staining were evident at other times during pregnancy and lactation the number of cells that stained for NADPH-d in the SON and PVN in rats on days 4, 12, 16, and 22 of pregnancy and on days 4, 12, and 20 of lactation was compared to that in virgin females. In a second experiment the influence of ovarian hormones on NADPH-d staining was assessed by comparing staining in the SON and PVN among ovariectomized animals exposed to either a steroid hormone replacement schedule that mimics late pregnancy (oestrogen and progesterone with progesterone removal), oestrogen alone, oestrogen and progesterone, or cholesterol alone. In the last experiment of this series staining was compared among ovariectomized animals given either oestrogen or cholesterol priming accompanied by oxytocin (OT) or vehicle infusion into the third ventricle for 7 days. The number of cells showing dense staining for NADPH-d in both the SON and PVN increased on days 12 and 22 of pregnancy and 4 and 12 of lactation compared to that observed in virgins. NADPH-d staining in these areas was also increased by both the steroid treatment that mimicked late pregnancy and chronic central OT infusion in oestrogen-primed animals. These data suggest that NADPH-d staining in the SON and PVN is increased at times when oxytocinergic cells are known to be active and that the hormonal state associated with late pregnancy is sufficient to increase NADPH-d staining.

Regulation of laminin chain gene expression by ovarian steroid hormones in uterine tissues of ovariectomized mice

To precisely analyze the role of ovarian steroids in the regulation of laminin chain gene expression in mouse uterine tissues, the ovariectomized mouse model was used. Ovariectomized mice received a single injection of steroid hormones and total RNA was isolated from whole uterine tissues. Messenger RNA levels of each laminin chain (A, B1, and B2) were determined by competitive RT‐PCR procedures. Estradiol decreased mRNA levels of laminin B1 chain about two‐fold, and B2 chain rather moderately. Estradiol‐induced inhibition of laminin B1 and B2 chain mRNA levels were completely blocked by pretreatment with estrogen receptor antagonist tamoxifen. Estriol, a short acting estrogen which cannot induce hyperplastic responses of rodent uterine tissues, also showed an inhibitory effect on B1 and B2 chain mRNA levels, while estrone, an inactive estrogen, failed to influence either B chain mRNA levels. Effects of steroids on A chain mRNA level were quite different from those on B chains. Laminin A chain mRNA level ...

499. - Role of ovarian steroids in modulating mood in premenstrual syndrome

499. - Role of ovarian steroids in modulating mood in premenstrual syndrome

Interleukin-1 beta and the endometrium: an inhibitor of stromal cell differentiation and possible autoregulator of decidualization in humans.

Interleukin-1 beta (IL-1 beta), which modulates cell proliferation and differentiation in a number of cell types, is present in human endometrial stromal cells. However, both the function of IL-1 beta in endometrium and the factors that modulate its expression in endometrial stromal cells are unknown. To examine the effects of IL-1 beta on decidualization, human proliferative endometrial stromal cells were cultured for 12 days in medium (Dulbecco's Modified Eagle's medium with 2% fetal bovine serum) containing 1 microM medroxyprogesterone acetate, 10 nM estradiol, and 1 microM prostaglandin E2 (PGE2) with and without IL-1 beta (17 pg/ml). Morphologic changes as well as release of prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1) were used as markers of decidualization. Morphologic analysis of cells exposed to IL-1 beta revealed incomplete decidualization. In addition, cells exposed to IL-1 beta released 40% less PRL and 85% less IGFBP-1 than cells cultured in the absence of IL-1 beta, and the PRL mRNA content of the IL-1 beta-exposed cells was decreased by 68%. A possible role for ovarian steroids in the modulation of IL-1 beta expression in the endometrium is suggested by the increase in IL-1 beta mRNA that occurs in late secretory endometrium and by the induction of IL-1 by estrogen and progesterone in the mouse uterus.(ABSTRACT TRUNCATED AT 250 WORDS)

The epidermal growth factor family in the mammary gland and other target organs for ovarian steroids.

The influence of ovarian steroids on the growth and development of the normal mammary gland and mammary tumors in laboratory rodents is well known to the research investigator, and has emphasized the need to understand the pathways by which these compounds exert their effects on target organs. The clinical significance of the ovaries to breast cancer was evident around the turn of the century, when ovariectomy was shown to ameliorate the course of this disease in some women [1]. The high incidence of breast cancer in women in the United States and the marked reduction in incidence of this disease in women ovariectomized an early age suggest a permissive or promotional role for ovarian steroids [2, 3, 4]. Similarly, the influence of age at menarche or menopause on breast cancer risk may be explained by the duration or extent of exposure to ovarian steroids [5]. The long-term use of estrogens to relieve postmenopausal symptoms in women has already been linked with an increased incidence of endometrial carcinoma [6]. This exogenous use of natural or synthetic ovarian steroids and their antagonists for the purposes of estrogen replacement therapy, contraception, or cancer treatment and prevention has become a major health issue and dilemma, especially when we consider the millions of women treated with this category of drugs.

Role of Ovarian Steroids in Development of Uterine Binding Sites for Prolactin in the Ferret1

The objectives of this study were to investigate 1) the presence of specific prolactin (PRL) binding sites in the ferret uterus, 2) the uterine location of 125I-labeled ovine PRL (oPRL) binding sites, 3) changes in uterine PRL binding sites during pseudo-pregnancy, and 4) regulation of PRL binding sites by ovarian steroids. Binding was determined through use of 125I-oPRL and 300-800 micrograms of protein from the 50,000 x g particulate fraction. Optimal binding occurred within 6 h at 25 degrees C. Scatchard analysis of saturation data revealed a single set of high-affinity (Kd = 4.99 x 10(-11) +/- 0.88 M), low-capacity (22.76 +/- 1.62 fmol/mg) binding sites. Analysis of hormonal specificity revealed that ovine growth hormone (oGH) cross-reacted with oPRL for the uterine binding sites, displacing 38% of the bound ligand. However, no inhibition of 125I-oPRL binding occurred in the presence of a 500-fold excess of bovine thyroid-stimulating hormone (bTSH), ovine LH (oLH), or ovine FSH (oFSH), suggesting hormonal specificity of the binding sites that are located in the luminal and glandular epithelium. Prolactin binding to ferret uterine membranes increased during the first half of pseudopregnancy, plateaued between Days 21 and 28, and then declined. The concentration of PRL binding sites in uteri of ferrets on Day 1 of pseudopregnancy was 4.91 +/- 0.42 fmol/mg of protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Progesterone increases Ca2+ currents in myometrial cells from immature and nonpregnant adult rats.

We examined the role of ovarian steroids in regulating Ca2+ channels in rat uterine smooth muscle. Ca2+ currents (ICa) in myometrial cells from nonpregnant adult rats and immature rats injected with either estrogen or progesterone or estrogen plus progesterone were measured with the whole cell patch-clamp method. ICa was more prominent in cells from diestrous rats than in cells from estrous rats. In cells from immature rats the ICa density was significantly greater in cells from progesterone-injected rats than in cells from estrogen-injected or noninjected rats. ICa in cells from rats injected simultaneously with progesterone and the progesterone antagonist RU-486 was not significantly greater than those from noninjected rats. These increases in ICa density are not the result of changes in ICa activation kinetics or voltage dependence, since both are unaffected by steroid injection. The kinetics and voltage dependence of the ICa current in cells from immature and nonpregnant adult rats are similar, suggesting that they represent a single population of Ca2+ channels.

P-251 - Role of ovarian steroids in the uterine fluctuation of prostaglandin F2α during the preimplantation stages of pregnacy in rats

P-251 - Role of ovarian steroids in the uterine fluctuation of prostaglandin F2α during the preimplantation stages of pregnacy in rats

Role of ovarian steroids on the catecholamine synthesis and release in female rat adrenal: [formula omitted] and [formula omitted] studies

In a previous report, we described the existence of an effect of ovarian steroids on the adrenal medulla activities of the enzymes involved in catecholamine (CA) catabolism. To complete that study, we have now examined the adrenal medulla activity of tyrosine hydroxylase (TH), the rate limiting enzyme of the CA synthesis, as well as the in vitro release of CAs from incubated adrenal medullas. The study has been performed with adrenal medullas from female rats with physiological (estrous cycle) or pharmacological (steroid treatment) alterations in their circulating levels of estrogens and progesterone. The in vitro release of CAs from incubated adrenal medullas of estradiol-treated rats was lower than that obtained in vehicle-treated animals. In consequence, the preovulatory increase of estradiol would be the responsible of the low in vitro release of CAs observed during the estrous phase of ovarian cycle. However, this steroid does not seem to affect the CA synthesis, since the adrenal medulla activity of TH was not altered after the estradiol treatment nor during the estrous cycle. On the contrary, progesterone treatment increased TH activity 24 h after the steroid injection. This effect was independent of estradiol. However, an estrogen-dependent increase in TH activity occured short-time after the steroid administration. Although progesterone by itself failed to modify the in vitro release of both CAs, it was able to reverse the estradiol-induced decrease in epinephrine release. In summary, estradiol seems to decrease the ability of the adrenal medulla to release CAs to the peripheral blood. without affecting the CA synthesis, whereas progesterone mostly affects TH activity, being its effects temporary and partially depending on estrogens.