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Novel Expression of Type 1 Corticotropin-Releasing Hormone Receptor in Multiple Endocrine Cell Types in the Murine Anterior Pituitary

Neuroscience Graduate Program (N.J.W., A.F.S.), Molecular & Behavioral Neuroscience Institute (N.J.W., R.T.E., A.F.S.), and Department of Biological Chemistry (R.T.E., A.F.S.), The University of Michigan, Ann Arbor, Michigan 48109-2200

Address all correspondence and requests for reprints to: Audrey F. Seasholtz, University of Michigan, Molecular and Behavioral Neuroscience Institute, Basic Science Research Building, Room 5035, 109 Zina Pitcher Place, Ann Arbor, Michigan 48109-2200. E-mail: aseashol{at}umich.edu.

The CRH family of ligands signals via two distinct receptors, CRH-R1 and CRH-R2. Previous studies localized CRH-R1 and CRH-R2 to a subset of anterior pituitary corticotropes and gonadotropes, respectively. However, numerous studies have indicated that stress and CRH activity can alter the secretion of multiple anterior pituitary hormones, suggesting a broader expression of the CRH receptors in pituitary. To examine this hypothesis, the in vivo expression of CRH-R1 and CRH-R2 mRNA was further characterized in adult mouse pituitary. Quantitative RT-PCR analysis demonstrated that CRH-R1 mRNA is greater than 100-fold more abundant than CRH-R2 mRNA in male and female mouse pituitaries. Dual in situ hybridization analysis identified cell-specific CRH-R1 expression in the anterior pituitary. At least half of the CRH-R1-positive cells expressed proopiomelanocortin-mRNA (50% in females; 70% in males). In females, a significant percentage of the cells expressing CRH-R1 also expressed transcript for prolactin (40%), LHβ (10%), or TSH (3%), all novel sites of CRH-R1 expression. Similarly in males, a percentage of CRH-R1-positive cells expressed prolactin (12%), LHβ (13%), and TSH (5%). RT-PCR studies with immortalized murine anterior pituitary cell lines showed CRH-R1 and/or CRH-R2 expression in corticotropes (AtT-20 cells), gonadotropes (T3-1 and LβT2 cells), and thyrotropes (TSH cells). Whereas CRH-R1 expression in corticotropes is well established, the presence of CRH-R1 mRNA in a subset of lactotropes, gonadotropes, and thyrotropes establishes these cell types as novel sites of murine CRH-R1 expression and highlights the pituitary as an important site of interaction between the hypothalamus-pituitary-adrenal and multiple endocrine axes.

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