Pulsatile hormone release as a window into the brain’s control of the anterior pituitary gland in health and disease: Implications and consequences of pulsatile luteinizing hormone secretion

An indisputable physiological feature of anterior pituitary hormone secretion is a pulsatile mode of signaling. The temporally pulsatile nature of anterior pituitary hormone release is endowed by episodicity of neuronal activation in hypothalamic control centers, which convey an intermittent stimulatory and/or inhibitory signal to responsive anterior pituitary cells. The anterior pituitary gland in turn responds with bursts of hormone secretion into the bloodstream, and thereby commands remote target tissues in an unique temporally organized fashion. In the case of the gonadotropic (LH and FSH) axis in men and women and in pubertal children, the intermittency of hypothalamic GnRH’s stimulation of gonado-trope cells is a critical determinant of sustained physiological function and is an absolute prerequisite to reproductive capability. Moreover, a host of pathophysiological derangements in various clinical states can be marked by disruption of the otherwise coordinated pulsatile release of gonadotropic hormones. Similarly, profound alterations in the burst-like mode of GH secretion occur throughout the human life span, and are typified by striking gender differences. Moreover, like LH, the pulsatile GH signal is profoundly modified by age (including changes within the first day of life and in adolescence, young adulthood, and older age), differences in body composition, degree of physical fitness, alterations in sleep and nutrient intake, and pathological disturbances in renal and hepatic function, among other conditions. Other neuroendocrine axes such as the corticotropic (ACTH) and lactotropic systems also manifest distinct physiological regulation of the burst-like mode of hormone secretion, and evince striking disturbances in conditions of disease. Importantly, because the frequency and amplitude of hormone secretory bursts are jointly controlled by hypothalamic (neuronal) effector pathways and systemic negative and positive feedback, an understanding of neuroendocrine pathophysiology offers unique insights into the brain’s regulation of the anterior pituitary gland and the pituitary gland’s susceptibility to feedback influences from peripheral target tissues. Here I review some of the salient recent concepts and developments in neuroendocrinology with a particular emphasis on physiological regulation and pathophysiological disruption of the pulsatile mode of LH secretion in girls, boys, women, and men.