Effects of an inhibin-like factor present in bovine and porcine follicular fluid on gonadotrophin levels in ovariectomized rats.
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Animals↗
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Levels of follicle-stimulating hormone, luteinizing hormone, oestradiol-17 beta and progesterone, and follicular growth in the pseudopregnant rat.
Throughout a period of pseudopregnancy the peripheral blood levels of progesterone, oestradiol-17 beta, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), as well as the size-distribution of ovarian antral follicles were estimated in the rat. The progesterone concentrations, as measured by a competitive protein-binding technique, exceeded metoestrous values (25 ng/ml plasma) from day 3 of pseudopregnancy onwards. The highest levels were found on days 6 and 8 (91 ng/ml). From day 8 onwards the levels decreased gradually but were still above metoestrous values on the day of pro-oestrus after pseudopregnancy. Concentrations of oestradiol-17 beta, as measured by radioimmunoassay, were within the range of those at metoestrus (about 5 pg/ml plasma) until day 10. Thereafter levels increased to a value of 57 pg/ml. Concentrations of FSH, measured by radioimmunoassay, were within the range of metoestrous values until day 10 (about 100 ngNIAMD-rat-FSH RP-1/ml serum), but declined to a level of 33 ng/ml on day 12. Concentrations of LH, measured by radioimmunoassay, were generally within the wide range of metoestrous values (9-60 ng NIAMD-rat-LH RP-1/ml serum), but concentrations found on days 4, 8 and 10 were significantly lower than those found on preceding or subsequent days. Histological determination of the number of follicles present in various volume-classes, showed an increase in antral follicles on days 1 and 2, comparable to the increase observed during metoestrus and dioestrus 1 of the normal cycle. There was no change in the follicles between days 3 and 10 and they resembled those of early dioestrus. Preovulatory growth had occurred by day 12. Injection of human chorionic gonadotrophin (HCG) on days 2, 4 or 6 showed that ovulation could be induced only in some of the larger follicles. On the basis of these results it is suggested that during pseudopregnancy the high progesterone levels present result in a decreased plasma LH level which is insufficient to cause full maturation of the follicles and to stimulate oestrogen secretion to the levels required for induction of an ovulatory surge of LH release.
Animals↗
Plasma hormones and pituitary luteinizing hormone in the rat during the early stages of pregnancy and after post-coital treatment with tamoxifen (ICI 46,474).
Plasma levels of oestradiol-17beta, progesterone and luteinizing hormone (LH) and pituitary levels of LH have been measured during the first 6 days of pregnancy, in normal rats and in rats receiving two doses of Tamoxifen (trans-1-(rho-beta dimethylamino-ethoxyphenyl)-1-2-diphenylbut-1-ene) on day 2 of pregnancy. In normal rats oestradiol rose strongly from early on day 3 to reach a peak concentration between 22.00 h on day 3 and 08.00 h on day 4. Progesterone concentrations rose from day 2 to reach peak values on day 3-4. In animals in which implantation was delayed 20-24 h by administration of Tamoxifen (0.1 mg/kg) orally on day 2 the increased level of plasma oestrogen was also delayed by 20 h. A higher dose of Tamoxifen (0.2 mg/kg) on day 2, which prevented implantation, completely eliminated the increase in plasma oestradiol. Neither dose of Tamoxifen affected the levels of progesterone. In both normal rats and rats treated with 0.1 mg Tamoxifen/kg, plasma LH levels declined by day 3 while pituitary levels rose steadily. There was no detectable change in either plasma or pituitary LH levels, accompanying the increase in plasma oestradiol in the normal rats. In animals receiving Tamoxifen (0.2 mg/kg), plasma LH increased to a maximum by day 4 while levels of pituitary LH decreased. The results show that the oestrogen "surge" of early pregnancy, occurs normally about midnight on day 3 and not late on day 4 as previously thought. It is considered that the plasma oestradiol peak in early pregnancy results from an increased release of FSH rather than an increased release of LH. Tamoxifen may owe part of its antifertility action to a capacity to inhibit the synthesis of oestradiol from progesterone.
Adrenalectomy↗
Changes in brain, pituitary and uterine cytoplasmic oestrogen receptors induced by oestradiol-17beta in the ovariectomized rat.
The oestrogen specific, high-affinity cytosol receptor receptor (HAR) from amygdala, anterior, middle and posterior hypothalamus, pituitary and uterus was studied in the ovariectomized rat. A single in-vivo injection of oestradiol-17beta produced significant changes in both the tissue HAR concentrations and the apparent dissociation constants (Kd) determined in vitro. Four hours after oestradiol-17beta treatment (20 mug/kg), the HAR concentration was depleted in all tissues except the posterior hypothalamus. A lower dose of oestradiol-17beta (4 mug/kg) produced similar changes in HAR concentration with the exception of those in the amygdala and posterior hypothalamus. Twenty-four hours after oestradiol-17beta, HAR concentrations had returned to pre-injection levels in all tissues except the uterus. The uterine HAR concentrations were raised after both doses of oestradiol-17beta. The apparent tissue cytosol Kd values were decreased by both doses of oestradiol-17beta. The results suggest that brain, pituitary and uterine oestrogen cytosol HARs react to plasma oestrogen in a manner predictable by the steroid receptor hypothesis. The oestradiol-17beta-induced differential effects upon the tissue cytosol concentration may contribute to the overall spectrum of action of oestrogen in the central and peripheral reproductive processes.
Amygdala↗
Steroid and prostaglandin concentrations in the plasma of pregnant ewes during infusion of adrenocorticotrophin or dexamethasone to intact or hypophysectomized foetuses.
Catheters were implanted into 16 ewes and their foetuses between days 110 and 124 of gestation. Hypophysectomy was attempted in eight of these foetuses. Continuous infusion of synthetic ACTH (10 microgram/h) or dexamethasone (1mg/24 h) into the foetus, starting between days 124 and 129, induced premature parturition. The concentration of progesterone in the maternal peripheral plasma decreased before parturition in all animals while the level of oestradiol increased in ewes with intact foetuses or in those in which hypophysectomy was incomplete. When hypophysectomy was complete, no increase in the maternal level of oestradiol occurred before delivery. The concentration of 13,14-dihydro-15-oxo-prostaglandin F2alpha increased in the peripheral plasma of ewes with intact or hypophysectomized foetuses infused with ACTH. It is suggested that an intact foetal pituitary gland is required for the rise in the level of oestrogen prepartum, but that this rise is not essential for increased prostaglandin production of parturition.
Adrenocorticotropic Hormone↗
Endometrial histology and circulating levels of medroxyprogesterone acetate (MPA), estradiol, FSH and LH in women with MPA induced amenorrhoea compared with women with secondary amenorrhoea.
Circulating levels of medroxyprogesterone acetate (MPA), estradiol, progesterone and gonadotropins were determined in 11 women on long-term treatment with depot-MPA (Depo-Provera DMPA) 150 mg i.m. every 12th week as a contraceptive. The women had amenorrhoea due to the treatment. Endometrial biopsy was performed one week after injection and at the end of the 12 week period. Blood samples were taken on the same occasions. The findings were compared with those in 12 untreated women having secondary amenorrhoea. MPA was still detectable in serum and the end of the 12 week period. Endometrial biopsies showed gestagenic effects in the second as well as in the first biopsy. No MPA was detectable in the untreated women with amenorrhoea, and no gestagenic effects could be demonstrated in their biopsies. The estradiol levels in the DMPA group were in the range of the early follicular phase of a normal menstrual cycle and showed a significant rise at the end of the 12 week period. On the last sampling occasion the estradiol levels did not differ from those in the untreated women with secondary amenorrhoea. The levels of progesterone and gonadotropins were in the range of the early follicular phase in both groups. These observations support that DMPA 150 mg i.m. every 12th week is a depotpreparation with prolonged effect, and inhibits ovulation and produces endometrial changes by means of biologically active serum concentrations throughout the 12 week period.
Adult↗
Midtrimester intra-aminotic administration of prostaglandin F2alpha in combination with an hyperosmolar urea solution: effect upon plasma levels of estradiol, progesterone, and human placental lactogen (HPL).
A study was undertaken in order to investigate the clinical observation that patients who underwent midtrimester abortion using intra-amniotic PG F2alpha in combination with hyperosmolar urea, always aborted a dead fetus. Ten Caucasian primigravidae, aged between 16 and 22 years old and whose pregnancies ranged between 14 and 23 weeks in duration, were studied. The patients were randomly divided into two equal groups. The one group received urea and PG F2alpha intra-amniotically whereas the other received PG F2alpha alone. Blood was drawn for measurement of plasma estradiol, progesterone and human placental lactogen (HPL) prior to injection of the abortifacients and at regular intervals thereafter for a period of 120 min. The five patients who received the combination regime of treatment (urea + PG F2alpha) showed a rapid decline in the plasma concentrations of these hormones and induction of abortion was followed by fetal death within 35 min in all cases. In contrast, the five patients who received intra-amniotic PG F2alpha alone, did not (with a single exception), demonstrate this rapid decline in the plasma concentrations of the placental hormones measured. Also with the same single exception, these fetuses, although stillborn, were alive two hours after inducing abortion.
Abortion, Induced↗
Uterine and ovarian estrogen receptor levels in climacteric women.
High affinity cytoplasmic estrogen receptors in the endometrium, myometrium and ovary of 15 climacteric women were studied. In addition, the concurrent serum estradiol and progesterone level of each woman was estimated and the endometrium examined histologically. The cytoplasmic estrogen receptor level of the endometrium and myometrium had remained extremely high in some cases several years after the menopause and in the presence of a completely atrophied endometrium. The lowest endometrial and myometrial estrogen receptor levels in pre-menopausal women were measured towards the end of the menstrual cycle. The eodometrial estrogen receptor level was roughly 2--3 times the comparable myometrial level. Estrogen receptors were also encountered in all cases in the cervical myometrium. The estrogen receptor levels of the ovary were low in all cases.
Adult↗
Estrogen-binding parameters of cytoplasmic and nuclear receptors in an established rat endometrial cell line and tumor.
We have consistently found receptors for estradiol in both the cytosol and nuclear extracts of a rat endometrial cell line and in transplantable tumors derived from this cell line. The equilibrium dissociation constants (Kd) and the rate constants for the receptor-estradiol interaction in these cells and tumors did not differ significantly from those of the cytosol receptor in the rat uterus. A mean Kd of 3 x 10(-10) M with a rate of association (Ka) of 3 x 10(5) M-1sec-1 and a rate of dissociation (Kd) of 1.5 x 10(-5) sec-1 were obtained for nuclear and cytosol receptors for both tumors and cells. For uterine cytosol, a Kd of 8 x 10(-10) M, ka = 2.8 x 10(5) M-1sec-1 and kd = 1 x 10(-5) sec-1 were obtained. Although no differences were seen in equilibrium and kinetic parameters for estradiol-17beta binding between the nuclear and cytosol receptors of tumors and cells, an apparent difference in the relative affinities of nuclear and cytosol receptors for estrone was detected. This suggests that the binding site in nuclear receptors may have been modified. Implications of this observation with regard to receptor translocation and the mechanism of action of sex hormones are being considered.
Animals↗
[Steroid receptors and hormonal receptivity. New pharmacological and therapeutic approaches applicable to the control of fertility].
The definition and main characteristics of the steroid hormone receptors are given. One may note a relationship between hormonal receptivity and the physiological changes in the concentration of the receptors in the target organs. The distribution of the various receptors is given in detail showing the existence of (a) different receptors for the same hormone in different target cells; (b) different receptors for different hormones in the same cells; (c) different receptors for the same hormone in the same cell. A new pharmacological approach is proposed based on differentiation of receptivities from which there results a dissociation of the therapeutic effects.
Drug Interactions↗
Effect of 3-(3,4-dihydro-6-methoxy-2-naphthyl)2,2-dimethyl pentanoic acid--an antifertility agent--on in vitro uptake of estradiol 17beta-6, 7(3)-H in rat uterus.
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Animals↗
Progesterone and estradiol patterns in women using an intrauterine contraceptive device.
Levels of progesterone, estradiol, LH, and FSH were measured in daily serum samples obtained from 4 subjects during a control cycle and during the first and fourth menstrual cycles after insertion of an intrauterine device (IUD). In addition, progesterone and estradiol were measured in serum samples obtained from 6 women 3, 4, or 5 months after IUD insertion, and from 6 women more than 1 year after IUD insertion. These measurements were compared to the data obtained from study of a large group of normal cycles. The results indicated that the IUD does not influence follicular maturation, time of ovulation, or corpus luteum function. The IUD did exert a local effect on the endometrium, causing the onset of menses to take place when steroid levels were higher than in control cycles.
Adult↗
Hormonal changes following hypophysectomy in humans.
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Androstenedione↗
Reserpine induced changes in the estradiol uptake by the pituitary and the uterus in ovariectomized rats.
Reserpine treatment produced a marked decrease of the in vitro binding of estradiol to the nuclear fraction of the uterus. A similar observation was made when reserpine was given into the incubation medium of uterine tissue. In contrast to these findings both in vitro and in vivo reserpine administration resulted in an increase of the estradiol binding to the nuclear fraction of the anterior pituitary in ovariectomized rats. The binding capacity of cytosol fraction after reserpine administration did not show significant alterations. In addition to these observations it is worth to mention that reserpine treatment resulted in a significant decrease of the estradiol-induced increase of uterus weight in ovariectomized rats.
Animals↗
Pituitary and ovarian response to acute stimulation with LH-RH in normal and anovulatory women.
The LH FSH estradiol and progesterone responses to acute stimulation with LH-RH were studied in 12 normal women with ovulatory cycles (4 in the initial follicular phase, 4 in the mid-follicular phase and 4 in the late follicular phase) and in two castrated women, two under hormonal contraception, two with ovarian amenorrhea, twelve with central amenorrhea of no detectable origin (6 with normal and 6 with low basal gonadotrophins), eleven anovulatory patients with pseudomenstruation, two with anorexia nervosa, and two with pituitary amenorrhea. Each woman received a rapid i.v. injection of 100 microgram synthetic LH-RH at 9:00 a.m. Serum levels of LH, FSH, estradiol and progesterone were determined by radioimmunoassay in samples collected before and 60, 120, 240 and 480 minutes after injection. The findings were : 1) A significant rise in estradiol and progesterone levels, in addition to LH and FSH elevation, in normal women; 2) A lack of ovarian steroid response in the castrated women and in ovarian amenorrheas, which suggests that the source of steroid response to stimulation is not extragonadal; 3) Significant differences in the responses of the four hormones to LH-RH in the women with central amenorrhea in comparison with the normal group with great variability of results; the steroid response in the presence of a positive LH response might correlate with the severity and/or prognosis of the disorder, a point deserving further study; 4) In anovulatory women with pseudomenstruation, LH responses for the most part normal, and particularly, progesterone responses.
Adult↗
Pure crystalline estradiol pellet implantation for contraception.
The subcutaneous implantation of estradiol pellets was found to be a simple and effective contraceptive method with good patient acceptance and minimal untoward effects. The pellets (25 mg each) were implanted through a Kearn's trocar into the abdominal wall, 2.5 to 5 cm above and parallel to Poupart's ligament. The regimen began with four pellets, and the dose was maintained or decreased by one pellet every 6 months (four, three, two, one). A potent progestogen was utilized monthly for induction of withdrawal bleeding. Altogether, 236 patients were followed for a total of 1,060 courses in 6,360 cycles (489,02 woman-years). Two pregnancies occurred during therapy. Pearl's index was 0.37. No significant alterations occurred in body weight and blood pressure. Glucose tolerance test, standard blood profiles, and Papanicolaou smears were normal during therapy. No cases of thrombophlebitis, blurred vision, headaches, gastric symptoms, or amenorrhea-galactorrhea were observed. The suppression of ovulation was confirmed by endometrial biopsies, basal body temperature, and serum follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in a selected group of patients.
Abdominal Muscles↗
[Antigonadotropic actions of prolactin. Study of 10 cases of women with hyperprolactinemia].
In order to determine the pituitary or ovarian site of the anti-gonadotrophic action of prolactin (PRL), ten women with hyperprolactinaemia were studied in the following way: 1) Repeated estimations of PRL, gonadotrophins (LH and FSH), plasma estradiol and progesterone during six weeks of treatment with bromocriptine. 2) Verification of the effects of estradiol benzoate on LH and FSH levels before and after normalisation of prolactin. 3) Exploration of the ovarian response to the administration of human menopausal gonadotrophin. Without it being possible to exclude any direct effect of prolactin on the ovary, it may be affirmed that the hormone decreases the sensitivity of the gonadotrophic cells to the positive feedback mechanism exerted by plasma estradiol.
Adult↗