STUDIES ON ANTIHORMONE SPECIFICITY WITH PARTICULAR REFERENCE TO GONADOTROPIC THERAPY IN THE FEMALE*

Abstract

PROTRACTED administration of extracts containing gonad-stimulating hormones will frequently result in the formation of antihormones (1). With the appearance of these hormone inhibitors two choices present themselves: either to discontinue therapy and await the disappearance of the antihormones, which usually is a matter of 2 to 3 months, or to administer a gonadotropin from another source. Whether or not a response to another gonadotropic extract in the presence of antihormones can be anticipated has received little clinical consideration. Animal experiments, however, provide leading information and while these studies are too extensive to review here, a good summary in table form is presented by Zondek and Sulman (2). In general, in the rabbit, pregnant mare serum gonadotropin will form antihormones which are specific in their antagonistic action. Sheep pituitary extracts, on the other hand, elicit antigonadotropins which are nonspecific in that they will antagonize the gonadotropic activity of human, ox, horse, pig, rat and rabbit pituitaries, of human chorionic gonadotropin and of pregnant mare serum. Numerous reports are also listed by Zondek and Sulman (2) to show that human chorionic gonadotropin will form antihormones in the rabbit and that these sera are capable of inhibiting human pituitary activity. It is evident from the animal experiments that the source of the gonadotropic extract is a factor in the problem of antihormone specificity. One might, of course, consider the results as being due to extracts which for the most part were not prepared for clinical use. This does not appear to be a determining factor, however, as it has been shown that the clinically used combination of sheep anterior pituitary extract and human chorionic gonadotropin (Synapoidin) will form antigonadotropins in the rabbit and that the serum will inhibit the gonadotropic activity of pregnant mare serum, human chorionic gonadotropin, human pituitary and rat pituitary (3).