In a series of hydrocortisone 17-esters, hydrocortisone 17-butyrate (HC-17B) has almost optimal lipophilicity resulting in a topical effect comparable to that of the fluorinated corticosteroids as measured in the McKenzie test on the human skin. In rats its systemic effects are weak, being in the order of those of hydrocortisone. In man systemic effects have been demonstrated, but no exact comparative data are available. Important factors controlling the intensity of systemic effects are: rate of liberation into plasma from the depot in the horny layer, rate of metabolic degradation, and rate of plasma clearance. In rats the main factor seems to be rapid clearance from plasma (t1/2 = 0.5 h) by selective concentration in the liver and, to a lesser extent, in the kidneys. Rapid hydrolysis by esterases in plasma and liver plays an additional role. In man hydrolysis by esterases appears to be rather slow; the rate of clearance from plasma is still unknown, whereas the absorption from the intact skin into the blood seems to be very slow (t1/2 = 25 h).
The sites and hormonal control of lipogenesis in hamster ear sebaceous glands are reported. Sebaceous lipogenesis was determined in ear biopsies by incubation with glucose and tracer concentrations of 14C-acetate in buffer. The 14C-labeled lipids were saponified, extracted, and determined by liquid scintillation counting. Histologically, the ears contained many sebaceous glands. The glands of male animals were much larger and more heavily lipid-stained than glands from females. Lipogenesis was almost entirely confined to the sebaceous glands in the dermal stroma. Lipogenesis was considerably higher in ear biopsies from male hamsters than from female, castrate male, or hypophysectomized male hamsters. In contrast to published data using hypophysectomized rats, where dihydrotestosterone potently and testosterone only weakly increased sebum secretion, both testosterone and dihydrotestosterone potently increased lipogenesis in the ears of hypophysectomized male hamsters. Dihydrotestosterone was somewhat more potent than testosterone in the hamster. Hypophyseal hormones do not appear to be essential for androgen stimulated lipogenesis in the hamster. In female hamsters, 5 alpha-androstane-3 alpha, 17 beta-diol, testosterone, dihydrotestosterone, 4-androstene-3,17-dione, and 5 alpha-androstane-3,17-dione produced dose-dependent increases in lipogenesis. From this and other studies, it is suggested that androgens other than dihydrotestosterone could be physiologically important in man and animals in stimulating lipogenesis in sebaceous glands.
Some derivatives of phenelzine have been shown to interrupt pregnancy in mice, when given after implantation, i.e. on days 7\p=n-\10. Pregnancy can be maintained in mice treated with these compounds and in mice hypophysectomized on day 7 by administration of suspensions of whole mouse pituitaries, of human chorionic gonadotrophin or of progesterone given with a basic concentration of oestrogen. Prolactin was ineffective in maintaining pregnancy. The action of the phenelzine derivatives could also be reversed by 0\m=.\5\p=n-\ \g=m\g.luteinizing hormone and by 0\m=.\05 \g=m\g. oestradiol. The compounds antagonized the action of progesterone in maintaining pregnancy in ovariectomized mice and this indicates that they act on the uterus. There may be, in addition, a more central action, e.g. on the ovary or on the pituitary but this would be masked by the peripheral (i.e. uterine) effect.
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