Localization and Regulation of a Functional GHRH Receptor in the Rat Renal Medulla

Abstract

To provide information about the kidney GHRH receptor (GHRH-R), we assessed its tissue and cellular localization, defined its pattern of expression in developing and aging rats, and studied the effects of GHRH on the regulation of GHRH-R mRNA levels and receptor internalization. In situ hybridization and ribonuclease protection assay demonstrated that GHRH-R mRNA is restricted to the Henle's loop (HL). GHRH-R mRNA levels were low in the medulla from 3- and 12-d-old male rats, increased significantly in that from 30- to 70-d-old rats, and decreased in that from 12- and 18-month-old animals. Compared with the GHRH-R mRNA profile obtained in the pituitary, these data support the concept of a tissue-specific regulation of GHRH-R. In HL cell cultures from 70-d-old rats, a 4-h incubation with 1-100 nM rat GHRH-(1-29)NH(2) reduced GHRH-R mRNA levels significantly. As anti-GHRH-R- (392-404) immunoreactivity was demonstrated in HL cells, internalization of [N(alpha)-5-carboxyfluoresceinyl-D-Ala(2),Ala(8), Ala(15),Lys(22)]hGHRH-(1-29)NH(2) in a time- and temperature-dependent manner and inhibition of this process by phenyl arsine oxide indicate that desensitization to GHRH involves both GHRH-R internalization and down-regulation of GHRH-R mRNA levels. Localization of a functional GHRH-R in HL and its regulation during development and aging suggest roles associated with cellular proliferation, differentiation, and/or water/electrolyte transport.

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).…”

Antagonist of growth hormone-releasing hormone induces apoptosis in LNCaP human prostate cancer cells through a Ca 2+ -dependent pathway

“…Although the expression of GHRH has been detected in various human normal and cancer cells, pituitary GHRHRs are virtually absent from almost every human nonpituitary tissue tested, including those in which GHRH had been previously shown to produce autocrine stimulation of cell proliferation (16)(17)(18)(19)(20)(21).…”

Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor

“…Although the expression of the GHRH peptide has been detected in various normal and malignant human tissues, including cancer cell lines, the receptor for GHRH (GHRHR) was absent from virtually every human nonpituitary tissue tested with the exception of renal tissue (12)(13)(14)(15)(16)(17). GHRHR was absent from tissues in which GHRH had been previously shown to produce autocrine stimulation of cell proliferation.…”