ACTH induction of the maturation of ACTH-sensitive adenylate cyclase system in the ovine fetal adrenal.
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Biomedical subjects
Publications and source records attributed to A Locatelli.
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The mechanism by which adrenal growth is achieved and steroidogenesis is stimulated in the fetal lamb during late pregnancy has been studied. Fetal plasma ACTH levels remained roughly constant between 14 and 3 days pre partum (298 +/- 38 pg/ml), then increased to a mean of 634 +/- 89 pg/ml. The rise in ACTH did not occur before the pre partum rise in cortisol. The increase in adrenal weight was achieved in three periods, one of DNA duplication between two phases of cellular hypertrophy. Cellular hypertrophy was accompanied by an important biosynthesis of membrane proteins. This development might partly explain the increased production rate of cortisol by the fetal adrenals during late pregnancy. At the same time, the number of ACTH receptors per 2 adrenals increased 5-fold. There was a close correlation between the levels of fetal plasma corticosteroids and the number of ACTH receptors during late pregnancy. It has been suggested that receptor modulation is one of the factors responsible for the enhanced sensitivity of the fetal adrenals to ACTH just before parturition. Preliminary results on the endocrine regulation of that development are also presented.
Hypophysectomy of the boar resulted in a rapid drop in plasma testosterone level. hCG injections (400 IU/day) considerably elevated testosteronemia (up to 16.41 ng/ml). This effect was obtained either in the days following the operation or several months after (up to 134 days). In the latter case, the effect was temporary because the testosterone level dropped again after 15 days of injections. The sexual target organs (epididymis, seminal vesicle, prostate and Cowper glands) underwent structural change which, in the epithelium, corresponded to fluctuations in testosterone level. These effects were less marked in the cauda epididymis than in other target tissues. In various target organs, the conjunctivomuscular stroma developed after the operation; it did not regress at all, or incompletely, when the epithelia were stimulated indirectly by hCG, and began to hypertrophy when the hCG was no longer effective. Variations in stromal reaction were organ-dependent. When the hCG was administered for more than 14 days, it seemed to have a desensitizing effect; these mechanisms have been discussed.
An androgen receptor has been characterized in the cytosol fraction of testes from hypophysectomized adult rams after in vitro labelling with [3H]testosterone. It can be distinguished from the testicular androgen-binding protein (ABP) and from the plasma 5 alpha-dihydrotestosterone-binding protein by electrophoresis on 3.25% acrylamide gels (Rx = 0.5) and on agar gels (anodic migration). It sediments in the 4S region in sucrose gradient containing 0.4 M KCl. Its complex with testosterone dissociates very slowly (t 1/2 = 29 h at 0 degrees C), and is destroyed by heating at 50 degrees C for 30 min and by pronase. Its relative affinities for steroids are 5 alpha-DHT greater than T greater than 5 alpha-androstanediols greater than cyproterone acetate greater than estradiol greater than progesterone. The number of binding sites is limited (about 20 fmoles/mg protein) and the apparent equilibrium dissociation constant (KD) is 5 x 10(-9) M.
Adult rams were hypophysectomized and treated for 20 days with testosterone (2 X 0.25 g/day), PMSG (2 X 300 i.u./day) or hCG (2 X 250 i.u./day), or for 40 days with testosterone (2 X 0.25 g/day). All treatments maintained a normal concentration of testosterone within the seminiferous tubules. Quantitative histological analysis showed that (1) the differentiation from A0 to A1 spermatogonia was maintained by PMSG or hCG but not completely by testosterone; (2) the transition from intermediate spermatogonia to primary spermatocytes was maintained only by PMSG but not by testosterone or hCG; (3) meiotic prophase and spermiogenesis were maintained by the three hormones but there were qualitative abnormalities in the spermatids. These results suggest that in the ram, the differentiation of renewing stem spermatogonia is under LH control and that the last stages of spermatogonial multiplication, from intermediate to B spermatogonia and to primary spermatocytes, are under the control of the FSH-like activity of PMSG.
Six adult rams were hypophysectomized and immediately injected with 0,5 g (group A) or 2 g (group B) of testosterone per day for 2 weeks. Three normal rams (group C) received the solvent only. The testosterone concentrations in the testis (ng/g) were the same in groups A (23 +/- 7) and C (22 +/- 4) and 3 times higher in group B (72 +/- 18). There was an uptake of testosterone by the testis of the two supplemented groups. In the Rete Testis Fluid, the testosterone concentration was normal with 0,5 g/day (29 +/- 0.6 ng/ml). The testicular weight was maintained by the two treatments. However, spermatogenesis was abnormal in both supplemented groups; meiosis and spermiogenesis occurred normally, but the efficiency of spermatogonial divisions, as shown by the number of leptotene and zygotene primary spermatocytes, was greatly reduced (85%). The results indicate that testosterone alone in the Ram is unable to support complete spermatogenesis, which is contrary to that found in the Rat.
In order to investigate the eventual role of XX/XY chimerism in freemartinism the vascular anastomoses between twin fetuses were surgically suppressed in litters with several fetuses, before the appearance of the first sexual anomalies. In three female fetuses isolated from their co-twins on days 37 and 45, the initial freemartin effect of gonadal and Müllerian inhibition was absent, in spite of an important XX/XY chimerism in the liver.
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The results of treatment with frusemide in 105 patients with established acute renal failure admitted during the past six years were reviewed and compared with control groups. Daily doses of 2,000 mg of frusemide administered from the day of admission onwards produced a significant increase in the number of patients who attained a diuresis and decreased the duration of oliguria.The reduction in the time spent in hospital and in the number of dialyses required suggests that the use of frusemide in these large doses is indicated in patients with severe established acute renal failure.
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