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We have been studying the endocrine system of elderly men with prostatic disorders, none of whom had any clinical or routine laboratory evidence of an endocrine disorder. The presence of prostate disease, so common in males over 60, may be an incidental finding, since we do not have data in age-matched controls. In 8 patients studied to date, 4 with prostate carcinoma and 4 with benign prostatic hypertrophy, decreased or absent pituitary luteinizing hormone (LH) reserve has been uniformly noted. No other abnormalities of pituitary function have been noted except that two patients had increased 24-h urinary total pituitary gonadotrophins, probably indicating primary testicular failure. Investigations included studies of growth hormone (GH) reserve by measurement of plasma GH levels following arginine stimulation (Merimee & Rabinowitz, 1969). Although 4 patients had Stage IV carcinoma of the prostate, none was cachectic and body weight in this group ranged from 2·5 to 16
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ABSTRACT
Progesterone receptor concentrations increased in fetal guinea-pig uterus in organ culture to as high as 13·15±1·22 pmol/mg DNA without any added steroid, although cytosol and nuclear oestrogen receptor levels were very low (0·41−1·92 pmol/mg DNA). Even after a 3-day exposure to 5×10−8 m-progesterone, which inhibits its own receptor (1·14±0·31 pmol/mg DNA), progesterone receptor levels rose to 8·58±1·39 pmol/mg DNA when progesterone was removed. This replenishment was inhibited by progesterone and 5α-dihydroprogesterone but was not affected by oestradiol, tamoxifen or dexamethasone. The incorporation of [3H]thymidine into nucleic acids was not decreased by progesterone so that its inhibition of its own receptor in the explants was not due to an inhibition of cell replication. Fetal uterine explants from oestrogen-primed fetuses, after an initial decrease in progesterone receptor, also showed a rise to 7 pmol/mg DNA on day 2 which could be decreased by exposure to progesterone and replenished by removal of this hormone (6–8 pmol/mg DNA), the entire process occurring without apparent oestrogen stimulation. Progesterone rather than oestradiol appears to be a key regulator of progesterone receptor synthesis in the fetal guinea-pig uterus, although oestradiol, along with other factors, may also be involved.
J. Endocr. (1985) 105,415–421
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The responsiveness of the uterus of the guinea-pig to oestrogen treatment was studied in the fetal and perinatal periods. Twenty-four hours after one dose of 1 mg oestradiol/kg body wt to the pregnant guinea-pig, there was no significant increase in uterine wet weight of the fetus but a sevenfold increase in the concentration of progesterone receptors. In the perinatal period, doses of 1,10 and 100 μg oestradiol led to as much as an 80% increase in uterine wet weight after 24 h in both 2- and 7-day-old guinea-pigs. On the other hand, levels of progesterone receptors in newborn animals showed a smaller increase (twofold) than that which occurred in the fetal uterus. In both fetal and newborn guinea-pigs, total oestradiol-receptor concentrations (both available and occupied binding sites) decreased significantly after treatment with oestradiol. It was concluded that the hormonal effect of oestradiol on progesterone-receptor synthesis can be expressed in the fetus and to an even greater extent than in the perinatal period over the same period of time. In the fetus, this response can be distinguished from the overall uterotrophic effect of oestradiol.
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The concentrations of unconjugated oestradiol-17β and oestrone have been measured by radioimmunoassay in the plasma of fetal, newborn and immature guinea-pigs. In fetal plasma, the values of oestradiol ranged from 15 to 50 pg/ml with no significant variations with gestational age except for an abrupt increase at the very end of gestation (148 pg/ml). Low concentrations of oestradiol were also found postnatally (from not detectable to 31 pg/ml) as well as in maternal plasma (22 pg/ml). The values of oestrone were consistently higher in all plasma regardless of age (43–164 pg/ml).
Oestrogen concentrations were also determined in the fetal uterus, lung, kidney and brain and were found to be as much as 60 times higher (per g tissue) than in plasma, especially in the fetal uterus which contained four to five times more than the other tissues. These data correlated well with a 20–90 times greater uptake of [3H]oestradiol by the fetal uterus compared with the other tissues after in-vivo administration of [3H]oestradiol to the fetuses. The selective retention of oestradiol was probably due to the presence of specific oestradiol binding in these fetal tissues, particularly in the uterus whose binding was 60–120 times higher than in the other fetal tissues. Thus, the levels of oestrogen in the circulation of fetal guinea-pigs are low, but the fetal uterus is capable of maintaining a higher concentration which may be important physiologically since oestradiol has been shown to evoke a biological response in the fetal guinea-pig uterus.
