Endocrine Abstracts (2009) 20 OC4.3

Homologous and heterologous in vitro regulation of pituitary receptors for somatostatin (SST), growth hormone (GH)-releasing hormone (GHRH) and ghrelin in a non-human primate (Papio anubis)

Jose Cordoba Chacon1,2, Justo P Castaño1, Rhonda D Kineman2,3 & Raul M Luque1,2

1Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain; 2Section of Endocrinology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA; 3Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.

Secretion of GH by pituitary somatotropes is primarily stimulated by GHRH and ghrelin and inhibited by SST through the activation of specific receptors (GHRH-R, GHS-R and Sstr1-5, respectively). However, we have previously shown that SST, at low doses, can also stimulate GH release, directly and specifically, in primary pituitary cell cultures from baboons (Papio anubis) and pigs. To determine whether these primary regulators of GH release can also regulate directly the expression of their receptors (GHRH-R, GHS-R and Sstr1-5) in primates, primary pituitary cell cultures from baboons were treated for 4 h with 10−8 M of GHRH or ghrelin, or with high (10−7 M) and low (10−15 M) doses of SST and GH release and expression levels of all receptors were assessed by ELISA and real-time-PCR. Results show that GHRH and ghrelin decreased the expression of their respective receptors (GHRH-R and GHS-R) while both peptides increased Sstr1, did not affect Sstr2 and only GHRH decreased Sstr5 mRNA levels. These effects of GHRH and ghrelin on receptor expression were mimicked by forskolin (adenylate cyclase activator) and TPA (PKC activator) respectively, indicating the regulation of receptor-isoform levels by GHRH and ghrelin involved distinct signaling pathways. In contrast, high SST doses did not alter GH release but increased expression of Sstr1, 2 and 5, and did not alter GHRH-R and GHS-R levels. Interestingly, low SST doses increased GH release and increased Sstr1 but decreased Sstr5 and GHRH-R mRNA levels, similar to that observed for GHRH. Taken together, our data show for the first time in a primate model that the primary regulators of somatotrope function (GHRH, ghrelin and SST) exert both homologous and heterologous regulation of their own receptor synthesis which is dose- and isoform-dependent, and would involve distinct signaling pathways.

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