Testosterone undecanoate (TU), either dissolved in arachis oil or as micro-crystal suspension, displays androgenic activity on oral administration to rats in the Hershberger test. The solution in arachis oil is more active than the crystal suspension. When [3H]TU is administered orally to rats, most of it is metabolized in the intestinal wall. The majority of the metabolites probably lose their undecanoate group and are absorbed via the portal vein. The non-metabolized [3H]TU and at least two metabolites are absorbed exclusively via the lymphatic system. One of these metabolites has been identified as 5\g=a\-dihydrotestosterone undecanoate (5\g=a\-DHTU).TU has no harmful effects on the liver of the rabbits on oral administration.It is well known that testosterone is inactive in man on oral administration (Foss 8c Camb 1939) while the widely used orally active androgen methyltestosterone may cause hepatic dysfunction in man: BSP retention (deLorimier et al f965) and jaundice (Werner et al. 1950; Foss 8c Simpson 1959). Foss 8c Simpson (1959) showed that testosterone propionate had no effect on liver function in man on parenteral administration. The present study describes the androgenic activity in rats, the effect on liver function in rabbits and the meta¬ bolism in rats of a new orally active androgen, testosterone undecanoate.

Progesterone-binding proteins from human, rabbit, sheep and guinea pig myometrial cytosol, all induced with oestradiol, as well as from pregnant guinea pig myometrium and plasma were investigated. The physico-chemical properties of the oestradiol-induced binding proteins were very similar in all the species studied. In all, 63 steroids were tested for their ability to compete with tritiated progesterone for the binding sites on these six proteins and their relative affinities were determined. The studies reveal that the ligand specificities of oestrogen-induced myometrial binding proteins from human, rabbit and sheep are rather similar, whereas that from guinea pig myometrium has different binding characteristics. The properties of the binding proteins from pregnant guinea pig uterus and plasma differ substantially from all of the induced proteins. It is clear from the different physico-chemical characteristics and binding specificities that the oestrogen-induced myometrial protein of the guinea pig is not the same as that which appears in the myometrium and plasma during pregnancy. The binding energies of the well bound progestational compounds were of the order of −12 Kcal/mole, half of which stems from the interaction of the steroid nucleus with the protein. The specific interaction of the protein with the two functional groups, the 3-keto-4-ene system and the acetyl side chain each contributed −3 Kcal/mole. In the case of the rabbit, sheep and human proteins a 17α-ethynyl-17β-hydroxyl function could replace the acetyl side chain. For a large number of steroids reasonable agreement existed between the degree of binding to the rabbit myometrial protein and in vivo biological activity (Clauberg-McPhail test) in the same species. The data suggest that as far as the binding aspect is concerned, the rabbit is an appropriate model for assessing the biological activity of compounds under development for human application. The in vitro binding system is also a useful tool to assess whether steroids need to be bio-activated before eliciting a biological response.

Sodium pentobarbital (Nembutal) is often used to block the pro-oestrous luteinizing hormone (LH) surge in rats. Nembutal is also known to lower body temperature. This study was designed to investigate whether Nembutal affected the time course of meiosis and timing of ovulation induced by exogenous hormones, and whether the possible effects of Nembutal on these processes were related to temperature. Gonadotrophin-releasing hormone (GnRH), the GnRH-analogue Ovalyse, or rat luteinizing hormone (LH) were administered to trigger resumption of meiosis and ovulation; Nembutal (35 mg kg-1 body weight) or saline was given 10 or 60 min later. Plasma profiles of LH were measured and Graafian follicles were studied histologically for meiotic progress and ovulation. Nembutal suppressed the spontaneous surge of LH at pro-oestrus and caused a long-lasting decrease in body temperature. If 1000 ng GnRH was given 2 h before the pro-oestrous LH surge, most of the oocytes had extruded a polar body 10 h later and most follicles had ovulated 14 h later. Nembutal given 1 h after GnRH delayed extrusion of the polar body and ovulation by about 2 h. Nembutal caused a similar delay in ovulation when it was administered after 100 ng of Ovalyse, and it also delayed meiosis when given after 1000 ng of LH. This effect of Nembutal was prevented if body temperature was maintained at 37 degrees C. The delaying effect of Nembutal on meiosis and ovulation induced by exogenous GnRH or LH is related to a long-lasting decrease in body temperature.

Lynestrenol is a potent oral pregestagen. The oral activities in the Clauberg and Corner & Allen tests are of the same order as that of subcutaneously administered progesterone. No effect was found in the tests for deciduomagenic activity in the mouse and for the maintenance of pregnancy in the rat. Lynestrenol has a marked inhibitory action on ovulation in the rat. This effect can be enhanced by low doses of oestrogen, which themselves are inactive in this respect. The main cause of this effect seems to be an inhibition of the development of the follicles. Lynestrenol is a weak oestrogen with an activity of about 1–2% of that of ethinyloestradiol. Its effects on fertilized ova in the rat are in agreement with what could be expected from its oestrogenic activity. There is little or no effect on nidation. Lynestrenol is a weak androgen, the oral activity in the rat amounting to 1/3–1/4 of that of methyltestosterone. 5. Acute and chronic toxicity studies demonstrate the absence of any general toxicity.