Administration Of Ethinyl Estradiol Research Articles

Modulation of Na +-H + exchange by ethinyl estradiol in rat colonic brush-border membrane vesicles

Prior studies by our laboratory have suggested that a relationship may exist between rat colonic brush-border membrane vesicular fluidity and Na +-H + exchange. To further explore this possible relationship, in the present studies the effects of ethinyl estradiol (17α-ethinyl-1,3,5-estratriene-3,17-β-diol) administration subcutaneously (5 mg/kg body wt. per day) for 5 days, on rat colonic brush-border membrane fluidity and Na +-H + exchange were examined. This treatment regimen has previously been shown to decrease the lipid fluidity of rat hepatic and rabbit small intestinal plasma membranes. In agreement with these prior studies, the present results demonstrate that this agent decreases the lipid fluidity of treated-rat colonic brush-border membranes compared to control membranes, as assessed by steady-state fluorescence polarization techniques using three different fluorophores. An increase in the cholesterol content and cholesterol/phospholipid molar ratio of treated-membranes appear to, at least partially, be responsible for the fluidity differences. Furthermore, examination of the kinetic parameters for amiloride-sensitive sodium-stimulated proton efflux in treated and control membrane vesicles, utilizing the pH-sensitive fluorescent dye, Acridine orange, revealed that ethinyl estradiol administration decreased the V max for this exchange mechanism, expressed in arbitrary fluorescence units, by approx. 25% but did not influence its K m for sodium. These data, therefore, lend further support to the contention that alterations in fluidity may modulate Na +-H + exchange in rat colonic brush-border membrane vesicles.

Organ specific modifying potential of ethinyl estradiol on carcinogenesis initiated with different carcinogens.

Estrogen has been shown to exert a modifying potential on carcinogenesis in various organs, and in particular the hormone-dependent tissues. The present experiments were carried out to determine the effects of post-initiation phase administration of ethinyl estradiol (EE) on tumor development in the liver, kidney, lung, thyroid, bladder and esophagus of male F344 rats. Animals were initiated by 2 weeks treatment with 0.05% N-bis(2-hydroxypropyl)nitrosamine (DHPN), 0.1% N-ethyl-N-hydroxyethylnitrosamine (EHEN), 0.03% N-nitrosopiperidine (NPD), 0.02% 2-acetylaminofluorene (2-AAF) or 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their diet or drinking water, and starting 1 week after initiation, they were given diet with or without a 0.001% EE supplement for 49 weeks, at which point the experiment was terminated. EE significantly increased the development of tumors of the liver (DHPN-, EHEN-, 2-AAF- and NPD-treated groups) and kidneys (EHEN-treated group) but inhibited their development in the lungs (DHPN-treated group) and urinary bladder (BBN-treated group). In the liver, EE also increased the development of glutathione S-transferase P type-positive lesions to various extents depending on the initiator used. EE administration was associated with a decreased incidence of esophageal hyperplasia in the EHEN-initiated group but an opposite increase in the NPD-initiated animals. No effect of EE was evident regarding thyroid lesions.

Effects of naloxone infusion on plasma levels of LH, FSH, and in addition TSH and prolactin in males, before and after oestrogen or anti-oestrogen treatment.

The inhibitory action of endogenous opioids on gonadotrophin release is now well documented. Since LHRH-producing neurons do not possess oestrogen-receptors, it is likely that some other compound mediates the negative feedback action of oestrogens on the gonadotrophin release in the male. To test the hypothesis that endogenous opioids are implicated in this negative feedback action in the human male, the opioid receptor antagonist naloxone (2 mg/h for 4 h) was infused into 7 normogonadotrophic oligozoospermic men before and after 6 weeks of treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) and 6 eugonadal transsexual males before and after 6 weeks of administration of ethinyloestradiol (EE) (10 micrograms three times a day). The effects of naloxone on TSH and prolactin (PRL) release were also studied. Naloxone administration resulted in a significant release of gonadotrophins, but not of TSH and PRL. Administration of oestrogen and anti-oestrogen did not significantly affect the response of gonadotrophins to naloxone infusion and no evidence of consistently antagonistic effects of oestrogen and anti-oestrogen on the naloxone-induced gonadotrophin release was obtained. This shows that endogenous opioids are probably not intermediary in the negative feedback control of oestrogens on gonadotrophin release in the human male. Surprisingly, in contrast to the eugonadal transsexual males, FSH levels in the oligozoospermic men did not respond to naloxone administration. As naloxone is thought to exert its action on gonadotrophin release via a disinhibition of endogenous LHRH release, this finding is unexpected. Exogenous LHRH administration leads to a normal response of FSH in normogonadotrophic oligozoospermic men. No plausible explanation for this finding can presently be offered.

Effects of ethinyl estradiol on intestinal membrane structure and function in the rabbit

Structural and functional properties of the small intestinal microvillus membrane were evaluated in the rabbit after administration of ethinyl estradiol, a synthetic estrogen with a demonstrated propensity to alter hepatic membrane lipid fluidity, and promote cholestasis. In the jejunum, no estrogen-induced changes in microvillus membrane total lipid, cholesterol or phospholipid content were observed. However, the ileal microvillus membrane in estradiol-treated animals demonstrates significant reductions vs. controls (per mg protein) in total lipid (0.55 μg vs. 0.89 μg) and phospholipid (206.7 μg vs. 304.91 μg) ( p < 0.001) content, as well as modifications in specific phospholipid species. The increase in the ileal microvillus membrane cholesterol: phospholipid molar ratio (0.65 vs. 0.51, p < 0.05) was associated with a significant decrease in membrane lipid fluidity reflected by an increase in fluorescence anisotropy measurements utilizing diphenyl hexatriene as the fluorophore ( r at 25 °C = 0.306 vs. 0.282, p < 0.05). Thermotropic lipid phase transitions, assessed by Arrhenius plots of both fluorescence data and ileal microvillus membrane p-nitrophenyl-phosphatase activity demonstrate that phase changes occur between and 24 and 28°C in both treated and untreated groups. Within the temperature range studied (40−10°C) no differences from control were observed in microvillus membrane alkaline phosphatase activity following estrogen treatment. These data therefore indicate that ethinyl estradiol-induced effects on microvillus membrane lipid composition and physical properties occur predominantly in the ileum and appear to be related, in part, to specific alterations in the availability of phospholipid following estrogen treatment.

Effects of continuous LHRH infusion on plasma levels of LH and FSH in males, before and after oestrogen or anti-oestrogen treatment.

In order to study the role of oestrogens on gonadotrophin release in the human male, LHRH was administered as an infusion at a constant rate of 0.5 micrograms/minute for 4 hours to 7 normogonadotrophic oligozoospermic men, 6 eugonadal male-to-female transsexuals and 9 eugonadal male volunteers. In agreement with in vitro data a biphasic release pattern of both LH and FSH was observed in eugonadal transsexuals as well as in normogonadotrophic oligozoospermic men. In the latter the release of LH was greater than in eugonadal transsexual males and volunteers, which points to a different functioning of the hypothalamic-pituitary unit in normogonadotrophic oligozoospermic men. On the other hand the FSH response to LHRH stimulation was normal in these men. Three months' treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) in the normogonadotrophic oligozoospermic men stimulated basal LH, FSH and testosterone (T) levels. The fact that gonadotrophin levels rose in spite of increased T levels, suggests a role of endogenous oestrogens in the negative feedback regulation of gonadotrophin release in these men. Upon TAM treatment the first phase, the plateau and the second phase of LH release were augmented, whereas only the plateau and the second phase of FSH release were increased. Six weeks' administration of the oestrogen ethinyloestradiol (EE) (10 micrograms three times a day) in the eugonadal transsexual males suppressed basal T and oestradiol (E2) levels without affecting basal gonadotrophin levels significantly. In EE-treated males the first phase of LH release tended to be lower, whereas the plateau of LH had decreased significantly. The second phase of LH was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of immunoreactive somatomedin-C levels by sex steroids.

Among 28 menstruating women tested once randomly during the cycle, somatomedin-C (Sm-C) values were lower in the 10 women in normal follicular phase than in the 10 women in normal luteal phase or the 8 women with hyperandrogenism. Among these 28 subjects, Sm-C showed a positive correlation with testosterone and a positive correlation of borderline significance with oestradiol. A positive correlation was also evidenced between Sm-C and in progesterone among the 20 women of this group who were not hyperandrogenic. In 5 other normal women investigated daily throughout an entire menstrual cycle, Sm-C concentrations were higher during days +4 to +9 of this cycle (luteal phase) than during days -3 to -8 (follicular phase). In another group of 21 healthy women, Sm-C values were increased during medroxyprogesterone acetate (150 mg trimestrially) treatment. In 7 normal men, Sm-C decreased during ethinyl-oestradiol (1 mg daily for 5 days) administration. These findings suggest that circulating Sm-C levels are modulated by variations of sex steroids which occur during the menstrual cycle as well as by pharmacological doses of oestrogens and progestagens.

Effects of iron overload on bile secretion and hepatic porphyrin metabolism in ethinyl extradiol-treated rats

We investigated the effects of ethinyl estradiol (5 mg/kg body wt daily for 5 days, orally) and/or iron sorbitol (50 mg/kg body wt daily for 5 days, i.m.) on bile flow, bile salt independent fraction (BSIF), hepatic ∂-amino-levulinate synthase (ALA-S) and uroporphyrinogen decarboxylase (URO-D) in female rats. Ethinyl estradiol administration was associated with a significant decrease of bile flow and BSIF and an increase in URO-D activity in comparison to control values. Iron alone did not modify biliary parameters, but significantly increased the activity of ALA-S. Combined treatment with ethinyl extradiol plus iron partially corrected the reduction of BSIF and restored the activity of ALA-S and URO-D to control levels. Thus iron appears to exert a partially protective effect against ethinyl estradiol-induced cholestasis. No porphyrinogenic effect was observed.

Isolation and estimation of gangliosides in discrete regions of the forebrain: effects of estrogen on regional lipid profiles

The main aim of the present study was to evaluate the neurochemical changes in the levels of gangliosides, total lipids, phospholipids, cholesterol, esterified fatty acids and triglyceride of the hypothalamus, hippocampus, amygdaloid nucleus, midline nuclei of thalamus, gyrus cinguli and olfactory bulbs following the intramuscular administration of ethinylestradiol (100 mcg) to each female rabbit daily for 30 days. Remarkable increment in the concentration of gangliosides was discernible in hippocampus, amygdaloid nucleus and olfactory bulbs. Interestingly, these levels showed significant decrement in the hypothalamus. The contents of total lipids, triglyceride and esterified fatty acids exhibited significant decrease in the hypothalamus. On the other hand, these levels showed a remarkable increment in olfactory bulbs with a significant elevation in the levels of phospholipids. The concentration of phospholipids was, however, markedly depleted in amygdaloid nucleus. The contents of esterified fatty acids exhibited decrement in hippocampus but the midline nuclei of thalamus showed increment. A significant elevation was also discernible in the levels of triglyceride in gyrus cinguli. The results suggest that the lipid contents are affected differentially in the various parts of the brain.

Gonadal dysgenesis induced by prenatal exposure to ethinyl estradiol in mice.

Daily oral administration of ethinyl estradiol (0.02, 0.2, or 2.0 mg/kg of body weight) to pregnant Jc1:ICR mice resulted in ovotestis and intra-abdominal testis with persistent Müllerian duct and Wolffian duct in male fetuses and ovarian hypoplasia in female fetuses when it was given from day 11 through day 17 of gestation (before gonadal differentiation in the fetus). The ovotestis consisted of testicular and ovarian portions. In the testicular portion, a few solid seminiferous tubules containing spermatogonia, some with pachytene nuclei with Sertoli cells and compact interstitial tissue including Leydig cells, were seen. In the ovarian portion, pachytene nuclei were seen. The intra-abdominal testis was smaller and contained more spermatogonia per tubule in cross section than the control testis. These findings suggest that in male fetuses ethinyl estradiol affects Sertoli cell differentiation resulting in suppression of Müllerian inhibiting factor. On the other hand, in the ovarian hypoplasia, the primordial follicles and follicular cells in a primordial follicle were significantly decreased in number, and the number of the degenerated primordial follicles was significantly increased. It seems likely that ethinyl estradiol affects the intimate contact between follicular cells and oocytes to cause degeneration of primordial follicles.

Effects of a Short Course of Estrogen on Mineral Metabolism in Postmenopausal Women*

Previous studies suggested that estrogen administration leads to an increase in circulating immunoreactive PTH (iPTH), thought to be secondary to a slight decrease in serum calcium resulting from inhibition of bone resorption. Using three different RIAs, we measured iPTH in serum from 10 postmenopausal women before and after 14 days of ethinyl estradiol administration. In 2 sensitive RIAs directed at the midregion of the PTH molecule, iPTH values fell or remained unchanged in each subject, with average decreases of 23% (P less than 0.001) and 28% (P less than 0.005) in the two assays. Total urinary cAMP, the tubular maximum for urinary phosphate excretion, and serum iPTH measured with the third RIA did not change after estrogen treatment. Fasting urinary calcium and hydroxyproline and serum calcium, phosphorus, albumin, alkaline phosphatase, and osteocalcin all decreased after treatment, and serum 1,25-dihydroxyvitamin D increased in each subject. In a second cohort of 5 women given ethinyl estradiol for 8 weeks, similar changes were found at 2 weeks, but there was a trend toward increasing serum iPTH, increasing total urinary cAMP excretion, and decreasing the tubular maximum for urinary phosphate excretion by 8 weeks. The increase in serum 1,25-dihydroxyvitamin D and the decrease in serum osteocalcin were again found after 2 weeks of estrogen and did not change further despite continued treatment. These results indicate multiple effects of a 2-week course of estrogen treatment on mineral metabolism in the absence of an increase in serum iPTH or several biological indices of PTH activity.

Effects of luteinizing hormone-releasing hormone (LRH) upon bioactive and immunoreactive serum LH in patients with Turner's syndrome before and after oestrogen treatment.

One daily dose of 0.05 mg ethinyl oestradiol was administered to 5 patients with Turner's syndrome (mean age +/- SEM = 16.4 +/- 0.7 years) for 10 days. The effects of acute stimulation with luteinizing hormone-releasing hormone (LRH) (0.1 mg iv) on biologically active and immunoreactive LH were analysed before therapy and at the end of oestrogen treatment. Bioactive LH (BIO-LH) was measured by a sensitive and specific in vitro bioassay based upon testosterone production by mechanically dispersed mouse Leydig cell preparations. Immunoreactive LH (RIA-LH) was evaluated by a double antibody RIA method. Prior to oestrogen treatment, LRH induced a prompt rise in BIO-LH and RIA-LH levels, which reached peak values at 30 and 45 min, respectively. After oestrogen treatment, a delayed response (with peak values at 120 min) was observed for both BIO-LH and RIA-LH. Before oestrogen treatment, the mean bioactivity to immunoreactivity (B/I) ratio of LRH-stimulated LH showed a significant decrease from basal values (P less than 0.05). In contrast, after ethinyl oestradiol administration the mean LH B/I ratio increased significantly from basal values in response to LRH (P less than 0.05). The mean relative maximum response (delta %) for BIO-LH was significantly higher (P less than 0.05) in oestrogen-treated than in untreated patients, whereas the mean BIO-LH delta area was significantly lower in the former group (P less than 0.01). Similarly, oestrogens decreased significantly the mean RIA-LH delta area (P less than 0.05), whereas they did not affect significantly the mean RIA-LH delta %. The results further emphasize that oestrogens may change the quality of circulating LH.

Influence of endogenous and exogenous oestrogens on posterior pituitary secretion in women.

Four normally menstruating subjects were studied throughout the menstrual cycle to investigate changes in plasma LH, arginine vasopressin (AVP), oxytocin (OT) and oxytocin associated neurophysin (NPOT). A clear mid-cycle LH peak was observed in each subject. Mean levels of AVP, OT and NPOT were 2.2 pmol/l, 1.1 pmol/l and 39 pmol/l, respectively. There were no significant differences between plasma levels during follicular, mid-cycle and luteal phases for each of these. Two further subjects with anovulatory cycles were studied in a similar way. In the first subject, with polycystic ovarian disease, posterior pituitary peptide levels were in the normal range, whereas the other subject, recovering from anorexia nervosa, had raised plasma levels of all posterior pituitary peptides (AVP 8.1 pmol/l, OT 1.8 pmol/l, NPOT 131 pmol/l, mean values) despite a normal osmolality. Administration of ethinyl oestradiol, 100 micrograms or 500 micrograms, had no effect of either AVP or OT, but 100 micrograms caused a marked rise in NPOT levels in all cases within 12 h (from mean 64 pmol/l to mean 196 pmol/l) and the levels remained elevated for 3 d.

Comparison of hepatic impact of oral and vaginal administration of ethinyl estradiol

The pronounced hepatic impact of oral ethinyl estradiol has been attributed by some to its so-called first-pass effect through the liver as only some 40% of ingested ethinyl estradiol reaches the systemic circulation. Others believe that ethinyl estradiol exerts its hepatic effects of its chemical composition, specifically its 17α-ethinyl group. In an attempt to resolve this controversy, a study was undertaken to determine whether vaginal administration of ethinyl estradiol can selectively reduce the hepatic effects of oral ethinyl estradiol. To compare the effects of oral and vaginal ethinyl estradiol, a group of postmenopausal subjects received either 5 μg of oral and 20 μg of vaginal ethinyl estradiol or 10 μg of oral and 50 μg of vaginal ethinyl estradiol in either sequence, respectively. Oral ethinyl estradiol was four to five times more potent than vaginal ethinyl estradiol. The potency ratios of the oral-vaginal ethinyl estradiol doses required to suppress follicle-stimulating hormone and luteinizing hormone were 4.4 and 3.2 and those to raise sex hormone-binding globulin binding capacity, corticosteroid-binding globulin binding capacity, and high-density lipoprotein cholesterol as well as lower low-density lipoprotein cholesterol were 3.5, 5.0, 4.2, and 4.2, respectively. These essentially equal oral-vaginal route potency ratios for both central nervous system and hepatic effects indicate that vaginal administration of ethinyl estradiol does not selectively reduce its hepatic impact in relation to its central nervous system effects. The pronounced hepatic effects of ethinyl estradiol are therefore attributed to its chemical composition.

Studies of the factors modulating antidiuretic hormone excretion in man in response to the osmolar stimulus: effects of oestrogen and angiotensin II

The aim of this study was to assess the influence of hormones known to regulate fluid and electrolyte balance on the release of antidiuretic hormone induced by raising serum osmolality. The stimulus provoked by the infusion of a 2.5% NaCl solution induces an increase of urinary [arginine-8]-vasopressin from 1.12 to 2.64 ng/h in men and from 1.65 to 7.27 ng/h in women as has been previously reported. These results were compared to those obtained in males infused with angiotensin II (AII) before and during a hypertonic sodium load and in males infused with hypertonic saline on the fourth day of administration of ethinyl-oestradiol. During the combined infusion of AII and then hypertonic saline, the mean hourly urinary excretion of AVP increased from 2.8 to 5.67 ng/h. Within each group the increase of urinary AVP was highly significant. The rise of urinary AVP during AII infusion was significantly different from the rise observed both in untreated males and untreated females, lying in between. The mean hourly excretion rate of AVP increased before and after hypertonic saline loading from 2.65 to 5.3 ng/h in males pre-treated with ethinyl-oestradiol. The significant difference observed between males and females is reduced when males treated with oestrogen were compared to female subjects. In each group plasma renin activity decreased to low values during the salt-loading test. During oestrogen treatment PRA and plasma renin substrate rose, while urinary aldosterone remained almost unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

The thyrotropin (TSH) profile in isolated gonadotropin deficiency: a model to evaluate the effect of sex steroids on TSH secretion.

This study evaluated the effect of estrogens and androgens on TSH secretion in hypogonadal male and female patients with isolated gonadotropin deficiency (IGD). The IGD subjects were clinically euthyroid and had normal circulating levels of thyroid hormones and T4-binding globulin (TBG). The patients were challenged with TRH (200 micrograms) in the untreated state, during treatment, and 1 month after cessation of hormonal replacement therapy. For the study, five females were treated with ethinyl estradiol (0.05 mg twice daily) for 21 days; after stopping for 7 days, the treatment schedule was repeated for another two cycles. The remaining female was given a similar regimen with conjugated estrogens (0.625 mg daily). Five males were treated with hCG (5000 IU twice weekly) for 3 months; two were treated with hCG and Pergonal. The female patients had significantly decreased basal TSH levels as well as impaired TSH responses to TRH. After 3 months of ethinyl estradiol treatment, there was a rise in TBG, total serum T4 and T3 levels and a decrease in T3 resin uptake; the free T4 index was unchanged. During estrogen administration, there was no change in basal TSH, but there was an increase in the peak TSH response to TRH, which became identical to that of the controls. Cessation of estrogen was associated with a reduction in releasable TSH, and the profile reverted to the pretreatment state. In addition, serum TBG levels, with the associated changes in thyroid hormones, also returned to normal. The male patients had TSH responses to TRH identical to those of the male controls. After 3 months of hCG treatment, there was a marked rise in serum estradiol as well as testosterone. Serum T4 was reduced without a change in T3, T3 resin uptake, or TBG. Furthermore, there was no alteration in the TSH response to TRH. On the other hand, the administration of ethinyl estradiol (0.1 mg daily for 2 weeks) to two male IGD subjects produced an increase in TBG. This was associated with elevation of serum T4 and T3 levels and reduction of T3 resin uptake. During estradiol administration, there was an increase in the TSH response to TRH. These data are compatible with the hypothesis that estrogens are required to maintain a normal TSH response to TRH in the female. However, testosterone may counteract the effect of estradiol, which may explain why normal males tend to have a lower TSH response to TRH than females.

Regulation of cytochrome P-450-dependent catechol estrogen formation in rat liver microsomes: Evidence for involvement of estrogen receptors

Experiments were conducted to evaluate whether estrogen 2-hydroxylase activity in liver microsomes, the main pathway for oxidative metabolism of estrogens in the rat, is regulated by administration of synthetic estrogens. Ovariectomized rats were treated with ethinylestradiol (EE), 100 μg s.c. for 3 days. Liver microsomes from EE-treated animals showed a 2-fold increase over control in estrogen 2-hydroxylase activity measured over a substrate concentration range of 0.5 to 50 μM. Double-reciprocal plots of enzyme activity as a function of substrate concentration were linear; apparent V max values were 2-fold greater in microsomes from EE-treated animals while apparent K m values for control and EE preparations were not different. Administration of the triphenylethylene antiestrogen tamoxifen (TAM), 100 μg s.c. for 3 days, did not affect microsomal catechol estrogen formation activity, and apparent K m and V max values were comparable with controls. When EE and TAM were co-administered, no increase in microsomal estrogen 2-hydroxylase was observed, and apparent K m and V max values were not different from either control of TAM-treated preparations. Thus, acute administration of EE was associated with a specific increase in the apparent V max of estrogen 2-OHase activity, and this effect was not observed when TAM was co-administered with the estrogen.

Pharmacodynamic effects of ethinyl estradiol in women using vaginal devices releasing small doses of levonorgestrel at a constant rate

Eight normally menstruating women were provided with vaginal devices releasing levonorgestrel (NOG) 4) at a constant rate of 20 μg/24 h. On day 71 or 72 following the insertion of the device, oral doses of 50 μg of ethinyl estradiol (EE) were administered daily for one week. Peripheral blood samples were drawn three times weekly during a pretreatment (control) cycle and from day 29 of the treatment period. The levels of progesterone (P), estradiol (E 2) and NOG were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by a steady state polyacrylamide gel electrophoresis and the percentage of binding of NOG, testosterone (T) and E 2 by equilibrium dialysis of diluted plasma. An endometrial smear and a biopsy were taken from each subject on 3 occasions, viz. during the control cycle (cycle day 20–22), during the period with the NOG-releasing device in situ (44–50 days after the insertion of the device), and on the 7th day of concomitant EE administration.

Feedback mechanism in sulpiride-induced hyperprolactinaemia.

Feedback of oestrogen on gonadotrophin release was studied in five normally cycling normoprolactinaemic women who were rendered moderately hyperprolactinaemic by oral administration of sulpiride (150 mg daily) for 11 consecutive days. Five patients with peptic ulcer, who had been given 150 mg of sulpiride for 3-18 months and had chronic marked hyperprolactinaemia were also studied. Ethinyl oestradiol (200 micrograms) was administered by mouth daily for 4 consecutive days and serum concentration of prolactin, luteinizing hormone (LH), follicle stimulating hormone (FSH) and oestradiol were measured by a double-antibody radioimmunoassay for 11 days. Oral administration of ethinyl oestradiol caused an initial decrease followed by a rebound of LH with a peak in all the women tested. The serum FSH levels showed only the initial decrease, followed by a slight rebound. Serum oestradiol levels decreased during oral administration of ethinyl oestradiol in all the women. The results of the present investigation suggest that oestrogen feedback effect on LH release is maintained in sulpiride-induced hyperprolactinaemic women as well as in women with normal cycles.

Circadian pattern of prolactin secretion in postmenopausal women receiving estrogen with or without progestin

The circadian rhythm of prolactin secretion was assessed in postmenopausal women before and after daily administration of ethinyl estradiol for 4 weeks given in the morning (am) or evening (pm) or in combination with a synthetic progestin, 17-medroxyprogesterone acetate. In response to am ethinyl estradiol, mean circulating levels of serum prolactin during sleep and awake phases of the day rose 2.5-fold compared to untreated control values. The sleep/wake ratios for serum prolactin were comparable prior to and after am administration of ethinyl estradiol. Altered time of administration, pm ethinyl estradiol or concomitant ethinyl estradiol and progestin treatment produced similar increases in mean prolactin levels, which were not different from the level observed during am administration of ethinyl estradiol. These findings indicate that estrogen replacement therapy, in a dosage recommended for treatment of the menopause, stimulated a sustained rise in serum prolactin over 24 hours. This enhanced release of prolactin was not influenced by the time of administration of estrogen or concomitant administration of 17-medroxyprogesterone acetate.

Estrogen-dependent changes in the functional interrelationships among neurons, ependymal cells and glial cells of the arcuate nucleus. Cytometric studies in the female albino mouse.

The synchronizing effect of ethinylestradiol (4 micrograms/g b.w.) on neurons of the arcuate nucleus 700-950 micrometers caudal to the posterior edge of the optic chiasma was studied by karyometry in 6-week-old albino mice during proestrus. The caudal portion of the arcuate nucleus was identified as the most estrogen-sensitive subdivision; all neurons showed an increase in their nuclear area (mean transect, profile area of the nucleus) 1 h following administration of ethinylestradiol. This hypothalamic region was selected for the subsequent electron-microscopic cytometric study to analyze functional interrelationships among neurons, ependymal cells and glial cells. Six and 12 days after ovariectomy no significant change in the nuclear area of neurons and ependymal cells was found 850-950 micrometers behind the posterior slope of the optic chiasma, but the neurons exhibited a decrease in the number of polyribosomes, the volume fraction (Vvmi) and the surface density of the inner membrane of mitochondria (Svmi). A similar decrease in Vvmi and Svmi was measured in the apical part of ependymal cells and in the pericapillary profiles of ependymal and glial cells, which was accompanied by a reduction in the surface density of ependymal processes extending into the ventricular lumen. In addition, no change of Vvmi and Svmi was seen in the basal subnuclear part of ependymal cells. This bipolar functional reaction of ependymal cells after ovariectomy is discussed as an indicator of ependymal control of neuronal activity by sequestering biologically active agents, e.g., transmitters of neurohormones, in their apical and basal extensions facing the ventricular surface or the pericapillary space.