ELSEVIER Molecular Brain Research 37 (1996) 175-180 MOLECULAR BRAIN RESEARCH Research report Age-related changes in the expression of corticotropin-releasing hormone receptor mRNA in the rat pituitary Sandra Ceccatelli a,*, Laura Calzfi b Luciana Giardino b a Institute of Environmental Medicine, Division of Toxicology, Karolinska Institute, S-17177 Stockholm, Sweden b Institute of Human Physiology, Medical School, University of Cagliari, Cagliari, Italy Accepted 24 October 1995 Abstract Hypothalamic corticotropin releasing hormone (CRH) controls the release of adrenocorticotrophic hormone (ACTH) from the pituitary gland, and therefore has a major role in the activation of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis function has been shown to be impaired in the neonatal period as well as in aging. Since corticotropin-releasing hormone receptor (CRHr) plays a crucial role in the regulation of HPA axis, using in situ hybridization histochemistry we have analyzed the rat pituitary for the presence of CRHr mRNA in the neonatal period and during aging. The results show an increase in CRHr mRNA in 3-day-old rats, with a progressive decrease within the first month. In the aging rat, we observed a down-regulation of the CRHr mRNA localized in the anterior pituitary, and viceversa, an increased signal in the intermediate lobe. Our findings demonstrate age-related changes in the expression of the CRHr mRNA in the pituitary, with a differential regulation in the anterior and intermediate lobes of aging rats. Keywords: In situ hybridization; Stress non-responsive period; Aging; Corticotropin releasing hormone receptor 1. Introduction Corticotropin-releasing hormone (CRH) is a 41-amino- acid peptide [24] widely distributed throughout the central nervous system [22]. The CRH cell population in the hypothalamic paraventricular nucleus (PVN) is part of the hypothalamic-pituitary-adrenal (HPA) axis. Activation of the HPA is a basic adaptive mechanism in response to stress. In fact, stressful stimuli elicit activation of the HPA with increased secretion of CRH from the hypothalamus, ACTH from the pituitary and thereby corticosteroids from the adrenal gland [15]. Receptor binding studies have shown CRH binding sites in the anterior and intermediate lobes of the pituitary with no staining in the neural lobe [1,4,27]. The HPA axis function has been shown to be impaired in the neonatal period as well as in aging• Ontogenic studies of the HPA have demonstrated the existence of a so-called stress non-responsive period (SNRP) in the neonatal rat, with decreased HPA's activa- tion in response to stressors [19]. The reason for this impairment is still controversial• The functioning of the HPA axis is also affected by * Corresponding author. Fax: (46) (8) 32-9041. 0169-328X/96/$15.00 © 1996 Elsevier Science B.V. All rights reserved SSDI OI69-328X(95)O0304-5 aging. In fact, an increased basal activity and significantly elevated basal concentration of glucocorticoids has been reported in old rats [5,8,10,17]. The stress response is also altered in old rats and is characterized by a prolonged increase of glucocorticoid plasma levels after acute stress [12,16,25]. The regulation of HPA axis hormone secretion during stress occurs at several levels of the brain- pituitary-adrenal system, the ACTH-secreting cells in the pituitary being one of the sites• In the present study we have used in situ hybridization to study the expression of CRHr mRNA in the pituitary of neonatal and old rats. The aim was to investigate whether possible changes in the expression of the CRHr mRNA could be related to the alteration of the HPA axis observed during development and aging• 2. Materials and methods 2.1. Animals Pathogen free Sprague-Dawley rats (n = 30; B &K Uni- versal, Sweden; IffaCredb, Italy) were used. The animals were housed under standard light/dark conditions with