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Some aspects on pituitary function in human and rat anovulatory cycles.

To investigate the anterior pituitary function of human anovulatory cycles, hormonal environments were analyzed in an animal experimental model and women with anovulatory cycles. A specific antiserum to hypothalamic luteinizing hormone-releasing factor (LH-RF) was prepared in rabbits. Intravenous injection of 1.0 ml of this antiserum to 4-day cycling female rats on the proestrous day blocked ovulation in the following cycles without changing regular estrous cycles on vaginal smear. Thus experimental anovulatory cycles were induced in antiLH-RF serum-treated rats. In this experimental model, LH surge on the proestrous evening was blocked but LH and FSH were maintained at the basal levels. In human anovulatory cycles, serum LH and FSH levels were also not significantly reduced except during the period of LH surge, and blood estradiol-17beta levels were similar to the levels of women with normal ovulation. Serum progesterone levels were higher in the normal women after the expected day for ovulation. These data may indicate that the anterior pituitary is able to secrete its gonadotropins without stimulation by LH-RF and this tonic discharge of gonadotropins would maintain the basal levels of ovarian secretion of steroids.

Adult

Influence of LH/FSH releasing hormone (LRH) on the basal secretion of gonadotrophins in relation to plasma levels of oestradiol, progesterone and prolactin during the post-partum period in lactating and in non-lactating women.

The pituitary responsiveness to LH/FSH releasing hormone (LRH) was studied in the puerperium in lactating and in non-lactating women. The response of both groups of patients to 25 mug LRH iv was tested 8-10 days, 15-17 days, and 29-32 days after a normal delivery at full term. The basal levels of FSH were low during the first 10 days after delivery. A rise was then observed, and about 4 weeks after delivery levels above or in the upper normal range of a normal follicular phase were recorded. The levels were significantly higher in the lactating group. When compared with the normal follicular phase, the relative increase in FSH basal levels was higher than the increase in LH basal levels in both groups of patients. The period of non-responsiveness of the pituitary to LRH was found to be of equal length in the two groups. In both groups the FSH response returned more rapidly than the LH response. About 2 weeks after delivery a reverse pattern of gonadotrophin response to LRH was seen with a FSH response that was greater than the LH response compared with what is generally observed in the various phases of the menstrual cycle in eumenorrhoeic women. This pattern was more pronounced in the lactating group about 4 weeks after delivery. Oestradiol levels were low and roughly equal on the three test occasions in each group, but in the non-lactating group there was a tendency to higher concentrations. Prolactin levels were highest about one week after delivery and then showed a tendency to decrease, and this was more pronounced in the non-lactating group. Progesterone levels were invariably low in both groups.

Adult

Pituitary gonadotrophin secretion during the first weeks of pregnancy.

A longitudinal study of basal plasma LH and FSH and their responses to 25 microng LRH iv as well as basal levels of oestradiol, progesterone, prolatin and HCG was performed every week in 3 women, pregnant after heterologous insemination, from conception until the 6th week of gestation. A comparative study was carried out in 7 women in cycles in which no conception occurred after insemination. All hormones were assayed with radioimmunoassay. LH was measured with a specific assay for native HL, which did not cross-react with HCG. A decrease in basal levels of LH and FSH as well as decreasing responses to LRH was found during the first 2 weeks of gestation. These changes did not differ from what was observed during the luteal phase in the non-conception cycles. One week later the basal FSH levels and the FSH response in the pregnant women showed a further decrease, while in the non-pregnant women, now reaching the early follicular phase, a rise in FSH basal levels occurred. The basal levels of LH and the LH response, however, did not differ from that found in the non-pregnant woment at this time. FSH basal levels remained below the lower normal limit in eumenorrhoic women from the 3rd week of gestation. By this time the FSH response was almost completely inhibited. The LH basal levels, however, remained above the lower normal limit in eumenorrhoic women, but the LH response to LRH progressively decrease and was completely inhibited by the 5th week of gestation. In the non-conception cycles the LH response varied with the levels of oestradiol in plasma. This was not found in the pregnant women as the decrease in gonadotrophin response occurred while oestradiol remained at mid-cycle levels during the first 4 weeks of gestation. Rather it seems that the increasing and continuously elevated level of progesterone, in the presence of appropriate levels of oestradiol, might be the main go nadal steroid responsible for the diminishing pituitary secretion. The contribution of HCG to the further decrease in gonadotrophin secretion after the 2nd week of pregnancy cannot be answered by the present studies. Prolactin remained at non-pregnant levels until the 6th week of gestation, and appeared to have no influence on the secretion of gonadotrophins during early pregnancy.

Adult

Examination of the role of FSH in periovulatory events in the hamster.

The need for endogenous FSH in the periovulatory events such as oocyte maturation, ovulation, luteinization, maintenance of luteal function and follicular maturation was examined in the cyclic hamster. A specific antiserum to ovine FSH, shown to be free of antibodies to LH and to cross-react with FSH of the hamster, was used to neutralize endogenous FHS at various times. Administration of this antiserum during pro-oestrus did not affect oocyte maturation and ovulation, as judged by the normality of the ova to undergo fertilization and normal implantation. It also had no effect on the process of luteinization or on the maintenance of luteal function as indicated by the normal levels of plasma and luteal progesterone during pro-oestrus and oestrus during the cycle and in pregnancy. All these processes were, however, disrupted by administration of an antiserum to ovine LH, thereby demonstrating their dependence on endogenous LH. Although FSH antiserum given at pro-oestrus did not prevent the imminent ovulation, it blocked the ovulation occurring at oestrus of the next cycle. This antiserum was effective in preventing the ensuing ovulation when given at any other time of the cycle until the morning of pro-oestrus. It is concluded that, in the hamster, high levels of FSH during pro-oestrus and oestrus are required for initiating maturation of a new set of follicles which are dependent on the trophic support of FSH throughout the cycle until the morning of pro-oestrus. Such follicles then appear to need only LH for subsequent ovulatory and associated processes.

Animals

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

Cyclic fluctuation in noradrenaline transmitter of the monkey oviduct.

Cyclic variations in noradrenaline of the sympathetic nerves ("short adrenergic neurons") innervating the smooth musculature of the oviduct have been determined by fluorescence histochemistry and fluorometric measurements in monkeys (Macaca mulatta). During the secretory phase there is more than twice as much neuronal noradrenaline in the oviduct compared with the proliferative phase. This suggests, that the system of adrenergic nerves in the primate oviduct is involved in the motility changes associated with alterations in the level of endogenous estrogen and progesterone during the menstrual cycle.

Animals

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

[Effects of lead administered during pregnancy to C57B1 mice].

Treatment of female mice with high doses of lead from different times of the gestation, induces abortion or retardation of growth of the embryos. When it is given from birth, it provokes important mortality in the youngs and a retardation of the postnatal growth. In most cases, lead administered from the first day of gestation delays slightly the development of the embryo and inhibits its implantation. It seems that a deficiency in the plasmatic progesterone levels is directly implied in this inhibition.

Abortion, Spontaneous

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

Postnidatory effects of luteinizing hormone releasing hormone (LHRH) in hamsters.

Whereas the administration of LHRH to pregnant hamsters has no effect during the prenidatory period, the hormone is effective in terminating pregnancy when given after implantation (days 6-10). The ED50 for pregnancy termination over this period approximates a dose of 0.35-0.4 mg b.i.d. When given to pregnant females in a second study, the effects of LHRH at this dose were completely reverse by minute doses of progesterone (30 microgram and above). Finally, administration of LHRH at 1.5 mg b.i.d., from days 6-10 was followed by daily sacrifice through day 12; bloods were sampled at autopsy for progesterone evaluation. Autopsies on days 7 and 8 showed few differences between controls and LHRH-treated hamsters, although decreased weights of the uterine/conceptus units signaled the initation of resorption. Significant LHRH-induced decreases in circulating progesterone were seen by day 9. Fetal resorption continued and was essentially complete by day 11, while progesterone levels continued depressed through the end of the study.

Animals

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