The long-term objective is to broaden existing knowledge of the nervous, hormonal and pharmacological influences that modulate secretory function at the cellular level, with a particular regard to events that bear on the problem of stimulus-secretion coupling. The secretory system selected for study is the intermediate lobe (or pars intermedia) of the mammalian pituitary gland whose endocrine cells constitute a virtually homogeneous population of melanotrophs. It is the only part of the adenohypophysis that is directly innervated by the brain. Moreover, this innervation is massive and involves neurones of diverse type containing various biogenic amines and peptides of different sorts. The spectrum of chemically different neurones identified in the intermediate lobe is already broad and will certainly expand if only because some of those observed have yet to be characterized. It is becoming increasingly evident that the innervation is extraordinarily complex with only some of the transmitters, or putative transmitters, identified. Moreover, the functions of only a few of these are even partly understood. Furthermore, the complexity of the situation is compounded by indications of striking qualitative differences in innervation and control among mammals: recent evidence from the rabbit indicates a control radically different from that in the rat on which current hypotheses are largely based. The massive and complex innervation of the intermediate lobe, albeit poorly defined, hints at a special need for the mammalian brain to regulate the secretory function of the melanotrophs. Yet, paradoxically, the function of these cells in the mammal is very poorly understood. What is clear, however, is that the individual melanotroph secretes a spectrum of peptides derived from the prohormone, proopiomelanocortin--notably endorphins, melanocyte stimulating hormones (MSH), and corticotropin-like peptides and there is rapidly accumulating evidence from various mammalian species including the human, pointing to the importance of these multiple secretory products in a variety of biological processes, among them pregnancy, fetal development, parturition, behavior, memory, reactions to stress, and some pathological conditions. The purpose of the proposed experiments is to obtain a better understanding of the cellular behavior of the melanotroph and its control by neuronal inputs and blood borne factors. The experiments, performed on isolated cells or neurointermediate lobes, mainly from rat and rabbit, involve the synthesis of evidence from two complementary lines of experiments, secretory activity on the one hand and electrical phenomena (including synaptic activity) on the other. Given the emerging evidence implicating melanotroph secretion in various physiological functions and pathophysiological conditions, the health relatedness of the proposed work is obvious.
