Hormone release by pituitary cell types is primarily regulated by stimulatory and inhibitory factors secreted by the hypothalamus. In turn, factors produced by the target organs controlled by the pituitary exert a feedback regulation on the corresponding pituitary cells. However, recent data indicate that, besides these factors, other mechanisms operate to finely tune pituitary function. These include both novel peripheral regulatory factors as well as intrinsic cellular elements. Regarding the first group, we will discuss our recent results on the interaction of adipocyte-derived adipokines involved in the regulation of metabolism and energy balance, with the pituitary. Thus, we have shown that adiponectin inhibits both basal GH and LH release as well as ghrelin-induced GH release and GnRH-stimulated LH secretion in rat pituitary cell cultures, wherein the adipokine also increases GHRH-R and ghrelin/GHS-R mRNA content while decreasing that of GnRH-R. We will also discuss the role played by the KISS1/KISS1R neuroendocrine system, which controls puberty and other reproductive functions, at the pituitary level. Specifically, our in vitro data using kisspeptin-10 (kp10) show that this peptide acts directly on pituitary somatotropes and gonadotropes to increase both free cytosolic Ca2+ and to stimulate modestly but significantly the release of GH and LH. Finally, we will consider the involvement of the different somatostatin receptors (sst1sst5) in the differential regulation of somatotropes by their classic inhibitor somatostatin and the somatostatin-related peptide cortistatin. We recently cloned two novel human and porcine truncated isoforms of sst5 (sst5B and sst5C) which are selectively activated by somatostatin (psst5B) or cortistatin (psst5C) and can interact with and functionally modulate full length sst5 and sst2. When viewed together, these data suggest that far from representing simple lineal models of regulation, pituitary cell types are controlled by complex multifactorial systems, comprising both intrinsic and peripheral factors, which will have to be uncovered in order to fully understand the precise regulation of the distinct pituitary cell types and, accordingly, their physiological role and pathological implications.
Support: BIO-139, P06-CTS-01705, and P07-CTS-3039-J.Andalucia, BFU2007-60180/BFI-MEC/FEDER, and CIBER Obesity&Nutrition-ISCIII. Spain.
25 - 29 Apr 2009
European Society of Endocrinology