Plasma concentrations of oestradiol-17beta were measured by a non-chromatographic radioimmunoassay during the oestrous cycle, after the s.c. injection of 2-5 or 10 microgram oestradiol benzoate (OB), or the s.c. implantation of Silastic capsules containing crystalline oestradiol-17beta. The profile of endogenous plasma oestradiol-17beta concentrations was similar to that reported by other workers, and lay between the concentrations produced by the low and high doses of OB. The rectangular pulses of increased plasma oestradiol concentrations, produced during the period of implantation of the Silastic capsules, were used to determine the time taken for oestradiol-17beta to exert its facilitatory effect on the gonadotrophin response to LH-releasing factor (RF). In animals ovariectomized at dioestrus, oestradiol, at concentrations similar to those reached during the peak of the spontaneous surge, first reduced the LH response. However, after 7 h, responsiveness increased significantly to reach a peak at 12 h. The FSH response was also greatest 12 h after ovariectomy. In animals ovariectomized at metoestrus the effect of oestradiol on the LH response was significantly less than in rats ovariectomized at dioestrus, and the FSH responses were lower than those in animals bearing empty capsules and examined at the same time after ovariectomy. These findings together with the effects of long-term exposure to sodium pentobarbitone are considered with respect to the possible mechanisms, including the priming effect of LH-RF, which may produce increased pituitary responsiveness after ovariectomy and exposure to oestrogen.
Spontaneous gonadotrophin release and the gonadotrophin response to LH releasing factor (RF) were studied in pro-oestrus, androgenized female and male rats. The animals were either intact or gonadectomized (about 32 h previously) and treated with various steroids. The gonadotrophin response (especially LH) was much lower in intact males and androgenized females than in pro-oestrous females. Oestrogen plus progesterone increased plasma gonadotrophin concentrations and responses in ovariectomized rats, but inhibited the increase in the plasma gonadotrophin concentration and the LH response which followed castration in males. As in the normal female, ovariectomy decreased the LH response but increased the plasma FSH concentration and response in the androgenized female; oestrogen and progesterone had relatively little effect. Apart from reducing the postcastration rise in plasma FSH, testosterone had no significant effect in gonadectomized male or female animals. These results show that the effect of steroids on the gonadotrophin response to LH-RF as well as the spontaneous secretion of gonadotrophin depends upon sexual differentiation of the hypothalamo-hypophysial system. Studies with various metabolites of progesterone indicated that the facilitatory action of this steroid could be due, in part, to a 5alpha-reduced derivative.
The effect of oestradiol-17beta (administered in Silastic capsules) on gonadotrophin secretion in long-term gonadectomized rats has been investigated. In female rats, a daily afternoon surge of LH occurred which could be blocked by administering sodium pentobarbitone at 13.00 h. This, together with the fact that there was no significant difference between the LH-response to LH-releasing factor in the morning compared with the afternoon, supports the view that the LH surges are due to a neural rhythm. There was no significant diurnal variation in plasma FSH concentration, but an apparent diurnal variation was disclosed by administering sodium pentobarbitone on alternate days. There was no diurnal variation in plasma gonadotrophin concentrations in male animals implanted with an oestradiol capsule, or in animals of either sex bearing empty capsules.
The proteins in saline washings from uteri of women at different stages of the menstrual cycle were examined by polacrylamide gel electrophoresis at pH 4-5 and pH 8-9, isoelectric focusing in polyacrylamide, and immunoelectrophoresis. The components present were mainly serum proteins but small amounts of uterine-specific proteins were also detected. Measurement of the activities of several glycosidases in uterine washings revealed that alpha-L-fucosidase, beta-N-acetylgalactosaminidase and beta-N-acetylglucosaminidase were elevated when compared with serum.
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