Female rats were subjected to 8 h of daily immobilization for 1, 3, 6, 10 or 15 days. Exposure for 3 days inhibited b.w. and induced adrenal enlargement as well as thymus involution; 6 days of stress elicited atrophy of the ovaries and hypophysis. During the later stages of the experiment, the animals showed a positive metabolic balance, and the initial weight alterations of the endocrine glands either tended to regress or were stabilized. On the 6th day, plasma corticosterone reached a peak which was maintained until the end of the experiment, whereas growth hormone (GH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) titers, as determined by radioimmunoassay, fell to 28, 39 and 55% of control values, respectively, following the 1st period of restraint; prolactin (Prl) decreased by 30% after the 3rd day. Thereafter, the plasma concentrations of these hormones remained low, around 40–60% of control levels, although FSH on The 6th day revealed a transient but significant elevation to 180% of initial values. After 15 days of 6-h-daily immobilization, an injection of LH-releasing hormone (LH-RH) and thyrotropin releasing hormone (TRH) induced dramatic increases of LH, FSH, Prl and thyrotropin stimulating hormone (TSH) in plasma. On the basis of the morphologic and hormonal changes, it appears that, in agreement with the concept of a shift in adenohypophyseal activity during severe chronic stress, repeated long-term restraint elicits an inverse relationship between the secretion of ACTH and that of GH, LH, Prl and, to a lesser degree, FSH. Such modifications do not seem to be associated with an inability of the pituitary to secrete these hormones, since it is still responsive to releasing factors.

No abstract

In the rat, pregnancy was affected by androstane derivatives (including three 9\g=a\-fluoro-4-androsten-3-one, 11-and 17-substituted), given orally in doses of 5 mg/100 g body weight from Days 3 to 10. Fluorohydroxyandrostenedione (FHA) and fluoxymesterone appeared to be 100% effective in suppressing fertility, while steroid U-6596 seriously disturbed gestation though not in all cases. Under similar experimental conditions, the abortifacient activity of FHA, fluoxymesterone and steroid U-6596 was respectively abolished, decreased or left unaltered after substitution of 9\g=a\-fluorine by hydrogen. The 5\ g=b\saturated homologues of FHA and fluoxymesterone, as well as 9\g=a\fluoro-17\g=a\-methyl-5\g=b\-androstane-3\g=a\,11\g=b\,17-triol, were totally ineffective in interrupting pregnancy. The relative antifertility potency of the fluorosteroids in rats roughly paralleled their uterotrophic activity in immature mice. Comparative studies showed that FHA (administered at the 5-mg dose level but from the 3rd to the 7th day of pregnancy) was more effective than the other two fluoroandrostenes tested. The abortifacient action of FHA was reduced when the dosage was decreased, the minimum 100% effective oral dose being 2\m=.\5 mg/100g body weight. In addition, this fluorosteroid also exerted some interceptive activity. Progesterone abolished the abortifacient effect of 2\m=.\5, but not of 5 mg, of FHA. Under identical conditions, prolactin had no such protective influence.

No abstract

In hypophysectomized rats, treatment with pregnenolone (pregn-5-en\x=req-\ 3\g=b\-ol-20-one) for 14 days prevented testicular atrophy, maintained spermatogenesis but did not counteract Leydig cell atrophy. Spermatogenic activity was abolished when a 16\g=a\-nitrile group was attached to the pregnenolone molecule, but pregnenolone-16\g=a\-carbonitrile (PCN) did not interfere with the spermatogenic effect of pregnenolone. These results are discussed in view of the fact that PCN inhibits intoxication with excess amounts of many steroids (e.g. anaesthesia due to heavy overdosage with progesterone or hydroxydione), whereas steroid hormones, administered at doses necessary to maintain physiological functions, are virtually resistant to this type of catatoxic action, which usually takes the form of enhanced metabolic degradation and/or substrate excretion.