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SUMMARY
The concentrations of luteinizing hormone releasing hormone (LH-RH) and luteinizing hormone (LH) were determined by radioimmunoassay in blood samples taken at intervals after the administration of different doses of synthetic LH-RH administered either intravenously or intranasally in healthy fertile men. Intranasal administration of LH-RH caused a dose-dependent increase of plasma LH with the peak occurring later than that after intravenous injection. The intravenous route was approximately 100 times more effective than the intranasal route in terms of the dose of LH-RH necessary to achieve an LH response of similar magnitude, but the route through the nasal mucosa seems a safe and convenient way for LH-RH administration. The characteristics of the disappearance curve, metabolic clearance rate and volumes of distribution of LH-RH in man are compared with those found by others.
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SUMMARY
After administration of oestradiol-17β to intact mature and immature rats, a decrease in the testicular concentration of specific oestradiol-binding sites was observed within 1 h. The binding capacity was replenished starting about 3 h after oestradiol administration and after 5 h the oestrogen receptor level had returned to control values. Exposure of intact animals to oestradiol-17β for longer periods (up to 24 h) did not result in an increase of receptor levels in testicular cytosol.
Mature animals which were hypophysectomized for periods of up to 10 days did not show a significant change in the number of specific oestradiol-binding sites in either total testicular tissue or dissected interstitial tissue. At 15 days or longer periods after hypophysectomy, an apparent increase in receptor concentrations in total testicular cytosol was observed due to a relative increase in the amount of interstitial tissue.
A specific oestradiol-binding protein is present in plasma of immature male rats aged less than 30 days. This plasma protein could also be demonstrated in the cytosol of testes of immature rats. In contrast to the cytosol receptor, which shows a moderate affinity for diethylstilboestrol (DES), the plasma protein did not bind DES. The sedimentation values of the plasma protein and the oestradiol receptor were 4 S and 8 S respectively. These differences in characteristics made it possible to demonstrate the presence of the oestradiol receptor in addition to the binding protein in testicular cytosol of rats from 14 days of age onwards. The nuclear receptor for oestradiol-17β could be demonstrated after incubation of testicular tissue of rats from 4 days of age onwards.
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Female Sprague–Dawley rats received a subcutaneous implant containing 2 mg oestradiol at the age of 7 weeks. One week later half of the rats treated with oestrogen and half of the rats in an untreated control group were irradiated with 2 Gy (200 rad) of X-rays. The content of oestrogen receptor of the mammary tissue and the concentration of prolactin in the plasma were studied at intervals of 2 months for a period of 14 months after this treatment. Oestrogen treatment resulted in a decrease in the content of oestrogen receptors in the mammary tissue of both irradiated and non-irradiated rats. In oestrogen-treated rats, plasma prolactin was raised 10–50 times and pituitary tumours were observed. Radiation had no additional effect on the oestrogen-receptor content of mammary tissue or the concentration of plasma prolactin. The changes in the oestrogen-receptor content of mammary tissue and the prolactin concentration of plasma preceded the development of mammary tumours. It is suggested that the synergistic action of oestrogen and radiation on rat mammary tumour development is the result of a stimulation by oestrogen and/or prolactin of the sensitivity of the mammary gland to ionizing radiation.
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Hypothalamic corticotrophin releasing factor (CRF) activity was determined in five dogs with spontaneous hyperadrenocorticism and in three control animals (one untreated, one treated with high doses of ACTH for 2 months and one treated with high doses of cortisone for 2 months). Hypothalamic CRF activity was low or undetectable in four dogs with spontaneous pituitary-dependent hyperadrenocorticism and was reduced in one dog with Cushing's syndrome due to an adrenocortical tumour. The results are compatible with a pituitary origin for pituitary-dependent hyperadrenocorticism in the dog but are not conclusive; direct information about the rates of hypothalamic CRF secretion is required.
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Department of Biochemistry (Division of Chemical Endocrinology), Medical Faculty, Erasmus University Rotterdam, Rotterdam, The Netherhnds
(Received 31 March 1976)
Studies on steroid hormone receptors in testicular tissue have previously revealed the presence of specific oestradiol receptors in interstitial tissue (Brinkmann, Mulder, Lamers-Stahlhofen, Mechielsen & van der Molen, 1972) and androgen receptors in tubular tissue (Hansson, McLean, Smith, Tindall, Weddington, Nayfeh, French & Ritzen, 1974; Mulder, Peters, van Beurden & van der Molen, 1974).
Recently methods for the preparation of isolated Leydig cells (Janszen, Cooke, van Driel & van der Molen, 1976) and Sertoli cells (Fritz, Rommerts, Louis & Dorrington, 1976) have become available. In the present study, binding of testosterone and oestradiol was investigated in such Leydig cell and Sertoli cell preparations.
Leydig cells were prepared, as described by Janszen et al. (1976), from adult rats 8 days after hypophysectomy. Sertoli cells were prepared, according to Fritz et al. (1976),
