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Effects of RMI 12,936, a synthetic antiprogestational steroid, in the rat.

The antifertility effect of RMI 12,936 in the rat is shown to be reversible. Luteal hypertrophy followed administration to pregnant, but not to pregnant hysterectomized rats. Similar hypertrophy followed administration to pseudopregnant, immature gonadotrophin-treated, and immature hysterectomized and gonadotrophin-treated rats, but the ovarian sensitivity to gonadotrophins was reduced or unchanged, suggesting that the ovarian hypertrophy is due to a direct ovarian action of RMI 12,936. Progesterone production on Day 15 of pregnancy by the enlarged ovaries following RMI 12,936 administration on Day 8 was not significantly different from control levels, but there was a highly significantly reduction on Day 9. An isomer of RMI 12,936, Tsomer 201, presumed to be 7alpha-methyltestosterone, was shown to have antifertility and uterotrophic activities in rats similar to those of RMI 12,936. Unlike RMI 12,936, however, Isomer 201 did show significant cross-reaction in the competitive protein-binding assay for progesterone and did not cause significant reduction in peripheral progesterone levels on Day 9 after administration on Day 8. From this and previous evidence it is concluded that RMI 12,936 inhibits progesterone synthesis, possibly by acting as an alternative substrate for ovarian delta(5)3-ketosteroid isomerase, and that the product is probably a competitive antagonist of progesterone at the receptor level.

Age Factors

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

Serum follicle-stimulating hormone, luteinizing hormone and progesterone concentrations in pseudopregnant rats treated with medroxyprogesterone acetate.

Pseudopregnant rats were treated early in pseudopregnancy with 1 or 10 mg medroxyprogesterone acetate (MPA). Serum FSH, LH and progesterone concentrations were determined on days 2-20 of pseudopregnancy in treated and control rats. The mean duration of pseudopregnancy was 13-5 days in the control animals, but when animals were treated with 1 mg MPA a dioestrous period of 21-4 days was observed. A period with leucocytic vaginal smears of at least 2 months was observed after treatment with 10 mg MPA. Injection with MPA on day 3 of pseudopregnancy did not affect the serum FSH concentrations during the subsequent days. The progesterone pattern was alike in the three groups of animals, i.e. the duration of the activity of the corpora lutea was similar in all groups. However, 10 mg MPA slightly lowered progesterone concentrations on days 4-8 of pseudopregnancy. In the saline-treated rats, LH concentrations decreased from days 2-5, and remained low until they increased after day 11 of pseudopregnancy. This increase was delayed until day 20 in the animals treated with 1 mg MPA, and was not observed in the animals treated with 10 mg MPA. It is argued that the increase of LH concentration at the end of pseudopregnency is not instrumental in the decrease of peripheral progesterone concentration but rather that the decrease in the progesterone concentration leads to the increase in the LH concentration.

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

Plasma hormone concentrations during the menstrual cycle of normal Chinese women.

The concentrations of progesterone, estrogens, luteinizing hormone and follicle stimulating hormone were measured in samples of plasma taken frequently during normal menstrual cycles in fourteen Chinese women. Each of the menstrual cycles was characterized by hormonal changes which were comparable to those previously reported in Caucasian subject.

Adult

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

Prenancy diagnosis in dairy cattle by progesterone concentration in milk.

Concentration of progesterone in whole milk was used to diagnose pregnancy in lactating dairy cows. Milk samples were taken 21 to 22 days postbreeding and analyzed for progesterone by radioimmunoassay. Progesterone in milk greater than 11 ng/ml, 8 to 11 ng/ml, and less than 8 ng/ml was used classify animals as pregnant, questionable, and not pregnant. In this classification for 123 cows, 67 were classified pregnant, 7 questionable, and 49 not pregnant. A comparison of progesterone diagnosis with actual calving results showed agreement of 73 and 98% for the cows classified as pregnant and not pregnant. Thirteen of 19 animals, in which there were discrepancies between diagnoses by milk progesterone and calving results, were not detected in estrus within 30 days after breeding. One animal classified not pregnant by milk progesterone was pregnant.

Animals

Plasma steroid concentrations in conscious and anesthetized rabbits.

The ovarian steroids, estrogen, androgen, and progestin, were measured in the peripheral plasma of adult female rabbits that were either conscious or anesthetized with sodium pentobarbital (nembutal) or halothane. Concentrations of estrogen, androgens, and progestin were determined before and at 10 and 45 min after systemic injection of either buffer or LH. In the controls androgen levels were significantly different between animals anesthetized with nembutal and halothane. However, the greatest treatment effect was noted in plasma progestin concentrations which were significantly elevated in halothane-anesthetized animals in comparison to the conscious and nembutal-anesthetized animals. Following LH, the androgen and progestin levels were significantly elevated over basal levels. Most likely the treatment effect observed in the controls was still present but was overridden by the increased release of steroids following gonadotrophin stimulation. This study suggests that halothane, in contrast to nembutal, does significantly elevate peripheral progestin and androgen levels.

Androgens