title: The expression of genes encoding opioid precursors and the influence of opioid receptor agonists on steroidogenesis in porcine adrenocortical cells in vitro.
abstract: Endogenous opioid peptides are involved in the regulation of the HPA-axis function and stress response mechanism. However, there is a scarcity of data on opioid involvement in the regulation of the adrenocortical endocrine function. This study was performed to: 1) establish the expression of proenkephalin, POMC and prodynorphin genes in the porcine adrenal cortex and test in vitro the influence of ACTH, angiotensin II, CRH and epinephrine on this expression, and 2) determine the effects of opioid receptor agonists on basal and ACTH- or angiotensin II-affected secretion of cortisol, aldosterone and progesterone by the cultured adrenocortical cells. Our experiment has demonstrated the presence of mRNAs for opioid precursors in cells isolated from the adrenal cortex and the significant effects of ACTH and angiotensin II, but not CRH or epinephrine, on adrenocortical transcription of the analyzed genes. Angiotensin II reduced the expression of the POMC gene but stimulated that of prodynorphin. In turn, ACTH decreased the transcription of prodynorphin. The study has also demonstrated the effects of selective opioid receptor agonists - DPLPE (delta), FK33-824 (mu) and U50,488 (kappa) - on adrenal steroidogenesis in pigs. Basal secretion of cortisol was enhanced after the activation of mu or kappa receptors, whereas ACTH-stimulated cortisol output was increased only by the mu receptor agonist. Angiotensin II-treated cells significantly decreased aldosterone secretion in the presence of the kappa receptor agonist. The present results suggest that opioid peptides are synthesized in the porcine adrenal cortex, indicating their involvement in the regulation of adrenal steroidogenesis through autocrine and/or paracrine interactions.
authors.affiliation: Department of Animal Physiology, University of Warmia and Mazury in Olsztyn, Olsztyn-Kortowo, Poland.
authors.forename: B E
authors.initials: BE
authors.lastname: Krazinski
authors.forename: M
authors.initials: M
authors.lastname: Koziorowski
authors.forename: P
authors.initials: P
authors.lastname: Brzuzan
authors.forename: S
authors.initials: S
authors.lastname: Okrasa
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006854:Hydrocortisone / Q000096:biosynthesis / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000235:genetics*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011957:Receptors, Opioid / Q000819:agonists*; D013256:Steroids / Q000096:biosynthesis*; D013552:Swine
chemical_list: D018847:Opioid Peptides; D011957:Receptors, Opioid; D013256:Steroids; D000450:Aldosterone; D011374:Progesterone; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D006854:Hydrocortisone