Endocrine Abstracts (2016) 41 GP121 | DOI: 10.1530/endoabs.41.GP121

Expression of dopamine (DA) D2 receptors (D2R) in corticotroph cells is responsible for the switch of hypothalamic regulation of ACTH secretion to DA in lactating rats

György M. Nagy1, Palma Fehér2, Ibolya Bodnár3, Luke Reid1, Zsuzsanna E. Tóth4, Miklós Vecsernyés2 & Bela E. Tóth2

1Ross University School of Medicine, Roseau, Dominica; 2Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary; 3EGIS Pharmaceuticals PLC, Budapest, Hungary; 4Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.

: Hypothalamic regulation of pituitary adrenocorticotropic hormone (ACTH) secretion switches to dopamine (DA) with a parallel loss of DAerg control of alpha-melanocyte-stimulating hormone (α-MSH) release in lactating dams. It has been also shown that dephosphorylation/inactivation of tyrosine hydroxylase (TH) in terminals of DA neurons at the median eminence is required not only for suckling-induced PRL release but also for ACTH responses. The aim of the present study was to further investigate the regulatory switch of ACTH with special emphasis on potential changes at the level of anterior lobe (AL) and the neuro-intermediate lobes (NIL) of the pituitary gland in lactating rats. AL and NIL cells obtained from ovariectomized (OVX) and lactating rats were cultured in vitro. Levels of PRL, ACTH and α-MSH were measured by RIA from culture media, with and without DA treatment. In cells obtained from OVX rats, ACTH secretion was not sensitive to DA, but both PRL and α-MSH were blunted. In contrast, on AL cells obtained from lactating rats, DA treatment resulted in an inhibition in both PRL and ACTH secretion but had no effect on α-MSH. ACTH immunohistochemistry and D2 DA receptors (D2R) in situ hybridization techniques were combined to investigate whether DA inhibition of ACTH secretion is due to the expression of D2R on corticotropes. It was found that expression of D2R was much higher in both the AL and the NIL of lactating dams compared to OVX animals. Combination of in situ hybridization with immunohistochemistry revealed co-localization of D2R with ACTH in a subpopulation of corticotropic cells of lactating animals. Therefore, the release of ACTH from corticotropes can be regulated by hypothalamic DA in lactating animals. This subpopulation of cells may also be responsible for the higher basal activity of the hypothalamo-pituitary-adrenal system and the stress hyporesponsiveness during lactation.