The release of pituitary hormones is regulated by hypothalamic neural and humoral input and also by negative or positive feedback signals from target tissues. The immune system is a target tissue of the pituitary gland. Recent studies have shown that interleukin proteins and thymic hormones may act a feedback signal at the hypothalamic-hypophyseal axis. The objective of this research grant application is to identify novel thymic peptides that stimulate the release of prolactin and GH from the anterior pituitary, and to investigate the effects of interleukin-6 (IL-6) upon pituitary hormone release. Neonatal thymectomy and congenital absence of the thymus are conditions that result in morphological alterations of the anterior pituitary gland. Since reductions in prolactin and GH are reported in the serum of athymic animals, we propose to culture the thymic stomal elements, which contain the hormone-secreting cells, and isolate from these cell preparations peptides that stimulate the release of prolactin and GH. Once isolated, we will investigate the signalling transduction pathway(s) activated by these thymic peptides in the anterior pituitary gland. Thymic peptide regulation of prolactin and GH release may act to affect immunogenesis, because both of these pituitary hormones stimulate immunocyte functioning. Interleukin proteins released by lymphoid cells in response to antigen alter the course of immunogenesis. Recently, these proteins have been implicated in the regulation of pituitary hormone secretion. Our preliminary studies show that IL-6, a cytokine with pleiotrophic activities, stimulate the release of prolactin and GH. We propose to investigate the specificity of this stimulation and the signalling transduction pathway(s) employed in the anterior pituitary. Since IL-6 acts in low concentration (pM), we hypothesize that it is produced in the pituitary and acts as a autocrine and/or paracrine factor. We will analyze pituitary cell conditioned medium for IL-6 activity and isolate enriched subpopulations of pituitary cells using unit gravity centrifugation to determine the cess type(s) that produces IL-6. Patients with cardiac myxoma and cervical carcinoma produce an IL-6 like factor; these conditions are associated with the production of autoantibodies. Since constitutive production of IL-6 may be responsible for the induction of an autoimmune state, the stimulation of immunopotentiating pituitary hormones by this interleukin needs to be acknowledged.
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