Restricted Presence of the Growth Hormone-Releasing Hormone Receptor to Somatotropes in Rat and Human Pituitaries

Abstract

Specific binding of growth hormone-releasing hormone (GHRH) to its plasma membrane receptor represents the first step of cellular signals leading to exocytotic GH secretion in the anterior pituitary. The GHRH receptor (GHRH-R) has been cloned and belongs to the secretin/glucagon/vasoactive intestinal peptide subfamilly of G-protein-coupled receptors. To study its characteristics in rat and human pituitaries and examine its cellular and subcellular localization, a site-directed polyclonal antibody recognizing the C-terminal portion 392–404 of the rat and human GHRH-R was used. Immunohistochemistry was performed on paraffin-embedded pituitary sections while ultrastructural immunocytology was done on frozen and Lowicryl-resin-embedded ultrathin sections. GHRH-R-like immunoreactivity was restricted to somatotropes and colocalized with GH in both rat and human tissues. No signal was detected in gonadotropes, lactotropes, corticotropes and thyrotropes. At the subcellular level, gold particles were associated with the plasma membrane (observed on ultrathin frozen sections), secretory granule membrane, cytoplasmic matrix, nuclear membrane and nuclear matrix. In the nucleus, gold particles were mainly observed at the junction between eu- and heterochromatin. The highest density of labeling was observed in the cytoplasm (55 vs. 45% in the nucleus), mainly in secretory granules (59% of cytoplasmic labeling) and the plasma membrane. These results support the hypothesis that GHRH-mediated actions in the pituitary are specific to somatotropes and that GHRH-R isoforms and/or ligand-receptor complexes are involved in intracellular trafficking, recycling processes and nuclear functions.

Cellular in vivo imaging reveals coordinated regulation of pituitary microcirculation and GH cell network function

“…Previous studies have described that GHRH receptors are restrictively expressed in GH cells (27)(28)(29), although we cannot exclude the possibility that low levels of receptor may be present in some other pituitary cell types. If GHRH receptors are completely restricted to GH cells, then local alterations in flow are most likely a consequence of secretory activity from stimulated GH cells.…”

Aging and Diets Regulate the Rat Anterior Pituitary and Hypothalamic Transcriptome

“…The overall impact on protein levels and cell functions will have to be addressed to further circumscribe the importance of the proposed mechanisms related to specific cell compartments or populations. Considering the impact of somatopause on several physiological functions and the greater abundance of somatotrophs in the anterior pituitary compared to other cell types [63], these cells represent a highly relevant target to confirm the importance of aforementioned mechanisms involved in aging and regulated by LTMCR.…”

International Union of Pharmacology. XXXV. The Glucagon Receptor Family

“…Using sensitive RT-PCR/Southern blotting assays, the GHRH receptor transcript has been found in an extremely wide range of rat tissues at low levels (Matsubara et al, 1995) GLUCAGON RECEPTOR FAMILY though the physiological significance of this broad expression remains unclear. GHRH receptor immunoreactive protein has been demonstrated only in the pituitary and the kidney (Morel et al, 1999;Boisvert et al, 2002).…”