Studies on LH bioactivity and gonadal receptors have provided insights into the regulation of pituitary-gonadal function of man, rhesus monkey and rat. Modulation of the frequency and bio:immuno rations (B:I) of plasma LH pulses also provides an important physiological mechanism for regulating the concentrations of effective LH available to the ovary and testis. The bioactivity of circulating LH appears to be rapidly modulated by gonadal steroids (i.e. normal men have higher B:I than cycling females; castration in rats decrease the B:I), possibly via changes in glycosylation. Also, the decrease in B:I of LH in castrated animals could be related to increased LH secretion rate. The B:I in older men with prostatic cancer as found to be low, indicating the potential importance of changes in B:I with age and sickness. Regression analysis showed an inverse relationship of B:I and plasma testosterone with age, and ill men over age 40 had lower B:I. These findings indicate that the qualitative nature of LH varies as a function of aging and illness in men. The abnormal nature of LH secreted with low B:I may be etiologically relevant in patients with impotence and normal immunoreactive pituitary hormones and LH periodicity, and low normal testosterone levels. The increased B:I during GnRH or clomiphene therapy in a patient with this type of disorder, and known to have pituitary calcification, indicated a functional relationship between pituitary GnRH exposure and the greater potency of secreted LH. The endocrine consequences of reversible endogenous estrogen excess on the pituitary-gonadal axis in man were analyzed in a detailed study of a patient with an estrogen-producing adrenal tumor. In this case, hypogondism was attributable to selective reduction in bioactive LH and low B:I ratio. The LH reduction could result from E2 action at the hypothalamic level to reduce GnRH secretion, and from direct effects on pituitary LH processing. We have also demonstrated that the adenine analog (4-Aminopyrazolo-(3,4-d)-Pyrimidine) has an inhibitory action on GnRN release from the hypothalamus, and are analyzing the relation of this effect to the mechanism of neurohormone secretion.
