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Effects of neuromedin U-8 on the secretory activity of the rat adrenal cortex: evidence for an indirect action requiring the presence of the zona medullaris

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Research in Experimental Medicine

Abstract

The acute effect of increasing concentrations (from 10−8 to 10−6 M) of neuromedin U-8 (NMU-8) on steroid secretion of rat adrenal gland was investigated in vitro by high-pressure liquid chromatography. The production of the following steroids was measured: pregnenolone (PREG), progesterone (PROG), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO). NMU-8 had no effects on either dispersed adrenocortical cells or fragments of adrenocortical autotransplants lacking medullary chromaffin cells. Conversely, NMU-8 exerted concentration-dependent secretagogue effects on adrenal slices, including both cortex and medulla. At all concentrations tested, NMU-8 increased the production of both PREG and total post-PREG steroids. The increase in total post-PREG steroid output induced by low concentrations of NMU-8 (10−8 M) was due to similar rises in the production of non-18-hydroxylated steroids (PROG, DOC and B) and 18-hydroxylated hormones (18OH-DOC, 18OH-B and ALDO); conversely, that provoked by higher concentrations of the neuropeptide (10−7 to 10−6 M) was almost exclusively caused by the rise in the yield of 18-hydroxylated steroids. The stimulating effect of NMU-8 on PREG output was blocked by both α-helical-CRH and corticotropin-inhibiting peptide, which are competitive inhibitors of CRH and ACTH, respectively. The following conclusions have been drawn: (1) NMU-8 affects adrenal steroid secretion indirectly by acting on the medullary chromaffin cells, which in turn may paracrinally stimulate the cortical ones; (2) at all concentrations tested, NMU-8, by stimulating the intramedullary CRH/ACTH system, causes a net rise in the activity of the early ratelimiting step of steroidogenesis, with the consequent increase in the output of the entire spectrum of post-PREG steroids; and (3) at higher concentrations (over 10−8 M), NMU-8 also elicits the release from chromaffin cells of a factor (not yet known) that specifically enhances 18-hydroxylase activity.

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Authors and Affiliations

  1. Department of Histology and Embryology, School of Medicine, PL-60781, Poznan, Poland

    L. K. Malendowicz, A. Markowska, M. Nowak & J. B. Warchol

  2. Department of Anatomy, University of Padua, Via Gabelli 65, I-35121, Padua, Italy

    P. G. Andreis, G. Neri & G. G. Nussdorfer

Authors
  1. L. K. Malendowicz
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  2. P. G. Andreis
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  3. A. Markowska
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  4. M. Nowak
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  5. J. B. Warchol
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  6. G. Neri
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  7. G. G. Nussdorfer
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Malendowicz, L.K., Andreis, P.G., Markowska, A. et al. Effects of neuromedin U-8 on the secretory activity of the rat adrenal cortex: evidence for an indirect action requiring the presence of the zona medullaris. Res. Exp. Med. 194, 69–79 (1994). https://doi.org/10.1007/BF02576368

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  • DOI: https://doi.org/10.1007/BF02576368

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