Role of luteinizing hormone-releasing factor (LH-RF) and LH on maintenance of early gestation in rats.
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Ten women were studied during the first post-partum week. Suckling for 20 min induced a marked increase in plasma prolactin, reaching a maximum within 0-25 min after the end of suckling and then returning to pre-suckling levels after 120 min. Suckling induced no changes in plasma thyrotrophin (TSH), growth hormone (GH) or follicle stimulating hormone (FSH). The iv injection of 200 mug of thyrotrophin releasing hormone (TRH) immediately after suckling resulted in an additional increase in plasma prolactin and a rise in TSH. When given 120 min after suckling TRH was followed by increased plasma levels of prolactin and TSH, which for both hormones were of a magnitude comparable to the TRH induced increment seen immediately after suckling. Thus, suckling did not inhibit the effect of TRH on the release of TSH. These studies indicate that TRH is probably not involved in the suckling induced increase in prolactin secretion. The mean plasma FSH level was below the limit of detection before and after suckling. Neither plasma FSH nor prolactin showed any appearant changes following the iv injection of 25 mug of luteinizing hormone releasing hormone (LH-RH), when given immediately after and 120 min after suckling. When given after suckling as indicated above, TRH induced no changes in plasma GH or FSH and similarly LH-RH was without influence on plasma GH and TSH.
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The possible participation of dopamine in the neural events that lead to the pro-oestrous surge of luteinizing hormone (LH) was investigated utilizing a dopaminergic ergoline derivative (lergotrile mesylate). Administration of reserpine (2.0 mg/kg, ip) to rats on the day of pro-oestrus depleted brain dopamine and norepinephrine and prevented the LH surge and ovulation. Administration of legotrile mesylate prior to or at the same time as reserpine prevented the inhibitory effects of reserpine on LH release and on ovulation in about half of the animals. When lergotrile mesylate was given on the morning of pro-oestrus, the LH surge was advanced. The results indicate that there is a dopaminergic component in the series of neural events that precede the surge of LH on pro-oestrus, and that the dopaminergic stimulus precedes the LH surge by about 4--5 h.
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Preovulatory LH surges were studied in rats with ovarian cycles of 4 days (4d-rats) and 5 days (5d-rats). In 5d-rats the maximal peak height was about twice that observed in 4d-rats, whereas in 4d-rats peaks occurred about 1-5 h later than in 5d-rats and were much less consistently timed. From experiments in which LH releasing hormone (LH-RH) was infused into pentobarbitone-blocked pro-oestrous rats, it was concluded that (a) differences between the two types of preovulatory LH surges originate within the central nervous system, and (b) pro-oestrous LH-RH secretion may not be restricted to the period in which increased LH levels in blood were found, but may exceed this period for a considerable time.
Effects of progesterone on production of androgen-dependent aggression-eliciting pheromones were investigated. Two groups of anosmic (non-fighting) castrated mice treated with testosterone or with testosterone and progesterone, respectively, were attacked to the same degree by intact, isolated (fighting) mice while control mice (castrated only) were attacked less. The findings support the ideas that progesterone may inhibit androgen-induced aggression via a neural and not via a somatic mechanism.
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.
Tne Holstein heifers acclimated to either -2.7 or 19.1 C were used to determine glucocorticoid concentrations in plasma following injection of adrenocorticotropin (200 IU). Environmental treatments did not change glucocorticoids following adrenococorticotropin. Adrenocorticotropin injection elevated mean glucocorticoids to 41.6 ng/ml plasma at -2.7 C and 42.8 ng/ml at 19.1 C. Adrenal response to adrenocorticotropin in Holstein heifers was not altered by low environmental temperature.
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Plasma renin activity (PRA), Growth hormone (GH) and immunoreactive insulin (IRI) were studied in seven healthy subjects during the ovulatory menstrual cycle and during the first and third cycles of oral contraception with 0.05 mg of ethinylestradiol and 0.100 mg or 0.125 mg of a new progestogen, 17 alpha-ethinyl-18-methylene-4-estren-17 beta-ol. The PRA level in the second half of the control cycle was significantly higher than in the beginning of the cycle. At the end of the treated cycles it was significantly higher than at the end of the control cycle. Neither GH nor IRI showed significant changes during the control cycle. GH was significantly higher at the end of the first and third treated cycles than at the end of the control cycle. IRI was significantly higher both in the beginning and at the end of the first treated cycle than the corresponding IRI levels in the control cycle. IRI at the end of the third treatment cycle was not significantly different from corresponding means at the end of the control cycle or the first treated cycle.
A considerable number of women receiving antiovulatory compounds or estrogens complain of weakness and fatigability, suggesting a state of clinical hypoadrenalism. For this reason, levels of plasma ACTH and plasma cortisol were determined in 25 women with such complaints both during treatment and at various intervals after cessation of this treatment. The results obtained showed that there was a significant inhibition of ACTH secretion during long-term treatment with antiovulatory compounds or estrogens, and in half of the cases, there was a delay in normalization of the pituitary-adrenal axis following interruption of the drug, supporting a state of transitory hypoadrenalism.
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In men suffering from prostatic cancer, i.v. administration of 12 g diethylstilboestrol diphosphate within 20 days resulted in a decrease of the LH serum level to about 50% (P less than 0.05), whereas the total testosterone level decreased to less than 5% (P less than 0.001) and the apparently free testosterone level to less than 2% of the initial values (P less than 0.001). Hence, the "systemic antiandrogenic effect" of oestrogen can be explained (1) by indirect inhibition of testicular androgen secretion via diminution of hypophyseal gonadotrophin secretion, (2) by direct inhibition of testicular androgen secretion and (3) by elevation of the capacity of testosterone binding beta-globulin.
In early pregnancy up the 7th week of pregnancy PGF2alpha was infused and 15(S)-methyl-PGF2alpha was applied i. m. to induce menstruation in 20 or 19 cases, respectively. In the tested form of application 15(S)-methyl-PGF2alpha is effective in 89 per cent of the cases and in 74 per cent complete abortion was achieved. PGF2alpha produced bleeding in 80 per cent only and complete abortion in 55 per cent. The differences in these two groups were not statistically significant. The steroid hormones estradiol and progesterone decrease in a successful application of PGs for induction of abortion and reach a value of 75 per cent at the onset of bleeding. The LH concentration in plasma becomes smaller too. In some cases there is a temporary increase in hormones shortly after starting treatment. The results could indicate that the considerable decrease in hormones before the onset of bleeding might be caused by an alteration of the corpus luteum, which is effective during early pregnancy.
The authors have studied the long-term effects of combined oestrogen-progestogen on the secretion of gonadotrophins and on ovarian function. Estimation of the radio-immune levels of the plasma concentrations of the pituitary luteinizing hormone (LH), of oestradiol (E2), of progesterone (P) and of 20 alpha hydroxyprogesterone (20 alpha OHP) and of testosterone (T) served as a base for this study. A test cycle and 8 cycles in which a combination of 50 micrograms of ethinyl-oestradiol and 0.5 mg of norgestrel were administered were studied in 4 normal volunteer women. A pituitary stimulation test using 50 micrograms of gonadotrophin "releasing factor" (LH-RH) was given during the 7th cycle. Ovarian stimulation using human menopausal gonadotrophins (HMG) was given during the 8th cycle of treatment in 3 of the women and in 3 other subjects. Pituitary secretion of LH and ovarian secretion of E2 and P are partially inhibited. Pituitary response to the injection of LH-RH stays normal but 5 out 6 patients had no response to stimulation by gonadotrophins. These results allow us to conclude that the lowering of production of gonadotrophins during treatment with combination oestrogen and progestagens is responsible for inhibition of ovarian activity, and that there is a delay before the latter respond to stimulation by either endogenous or exogenous gonadotrophins.