Skip to main content
SpringerLink
Log in

Evidence that an extrahypothalamic pituitary corticotropin-releasing hormone (CRH)/adrenocorticotropin (ACTH) system controls adrenal growth and secretion in rats

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Within two weeks, hypophysectomy induced in rats a striking decrease in the level of circulating ACTH (the concentration of which was at the limit of sensitivity of our assay system), coupled with a net reduction in the plasma corticosterone concentration and an evident adrenal atrophy. Zona fasciculata, the main producer of glucocorticoids, was decreased in volume, due to a lowering in both the number and average volume of its parenchymal cells. Subcutaneous ACTH infusion (0.1 pmol·min-1), administered during the last week following hypophysectomy, restored the normal blood level of ACTH and completely reversed all effects of hypophysectomy on the adrenals. Subcutaneous infusion for one week with α-helical-CRH or corticotropin-inhibiting peptide (1 nmol·min-1), which are competitive inhibitors of CRH and ACTH, evoked a further significant lowering of plasma corticosterone concentration and markedly enhanced adrenal atrophy in hypophysectomized rats. These findings strongly suggest that an extrahypothalamic pituitary CRH/ACTH system may be involved in the maintenance of the growth and steroidogenic secretory activity of the rat adrenal cortex.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aguilera G, Millan MA, Hauger RL, Catt KJ (1987) Corticotropin-releasing factor receptors: distribution and regulation in brain, pituitary and peripheral tissues. Ann NY Acad Sci 512:48–66

    Google Scholar 

  • Andreis PG, Neri G, Nussdorfer GG (1991a) Corticotropin-releasing hormone (CRH) directly stimulates corticosterone secretion by the rat adrenal gland. Endocrinology 128:1198–1200

    Google Scholar 

  • Andreis PG, Neri G, Belloni AS, Mazzocchi G, Kasprazak A, Nussdorfer GG (1991b) Interleukin-1β enhances corticosterone secretion by acting directly on the rat adrenal gland. Endocrinology 129:53–57

    Google Scholar 

  • Andreis PG, Neri G, Mazzocchi G, Musajo F, Nussdorfer GG (1992) Direct secretagogue effect of corticotropin-releasing factor on the rat adrenal cortex: the involvement of the zona medullaris. Endocrinology 131:69–72

    Google Scholar 

  • Belloni AS, Neri G, Musajo FG, Andreis PG, Boscaro M, D'Agostino D, Rebuffat P, Boshier DP, Gottardo G, Mazzocchi G, Nussdorfer GG (1990) Investigations on the morphology and function of adrenocortical tissue regenerated from gland capsular fragments autotransplanted in the musculus gracilis of the rat. Endocrinology 126:3251–3262

    Google Scholar 

  • Bornstein SR, Ehrhart M, Scherbaum WA, Pfeiffer EF (1990) Adrenocortical atrophy of hypophysectomized rats can be reduced by corticotropin-releasing hormone (CRH). Cell Tissue Res 260:161–166

    Google Scholar 

  • Bornstein SR, Ehrhart-Bornstein M, Usadel H, Böckmann M, Scherbaum WA (1991) Morphological evidence for a close interaction of chromaffin cells with cortical cells within the adrenal gland. Cell Tissue Res 265:1–9

    Google Scholar 

  • Bruhn TO, Engeland WC, Anthony ELP, Gann DS, Jackson IDM (1987) Corticotropin-releasing factor in the dog adrenal medulla is secreted in response to hemorrhage. Endocrinology 120:25–33

    Google Scholar 

  • Brusbridge NJ, Grossman AB (1991) Stress and the single cytokine: interleukin modulation of the pituitary-adrenal axis. Mol Cell Endocrinol 82:C209-C214

    Google Scholar 

  • Canick JA, Purvis JL (1972) The maintenance of mitochondrial size in the rat adrenal cortex zona fasciculata by ACTH. Exp Mol Pathol 16:79–93

    Google Scholar 

  • Dave JR, Eiden LE, Eskay RL (1985) Corticotropin-releasing factor binding to peripheral tissue and activation of the adenylate cyclase-adenosine 3′,5′-monophosphate system. Endocrinology 116:2152–2159

    Google Scholar 

  • Edwards AV, Jones CT (1988) Secretion of corticotropin releasing factor from the adrenal during splanchnic nerve stimulation in conscious calves. J Physiol (Lond) 400:89–100

    Google Scholar 

  • Fehm HL, Holl R, Spatschwalbe E, Born J, Voight KH (1988) Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin. Life Sci 42:679–686

    Google Scholar 

  • Fujita H (1972) On the fine structure of alteration of the adrenal cortex in hypophysectomized rats. Z Zellforsch 125:480–496

    Google Scholar 

  • Gallo-Payet N, Poithier P, Isler H (1987) On the presence of chromaffin cells in the adrenal cortex: their possible role in adrenocortical function. Biochem Cell Biol 65:588–592

    Google Scholar 

  • Gwosdow AR, O'Connell NA, Spencer JA, Cumar MSA, Agarwal RK, Bode HH, Abousamra AB (1992) Interleukin-1-induced corticosterone release occurs by an adrenergic mechanism from rat adrenal gland. Am J Physiol 263:E461-E466

    Google Scholar 

  • Gwynne JT, Strauss JF III (1982) The role of lipoproteins in the steroidogenesis and cholesterol metabolism in steroidegenic glands. Endocr Rev 3:299–329

    Google Scholar 

  • Hashimoto K, Murakami K, Hattori T, Niimi M, Fijimo K, Ota Z (1984) Corticotropin-releasing factor (CRF)-like immunoreactivity in the adrenal medulla. Peptides 5:707–712

    Google Scholar 

  • Hinson JP (1990) Paracrine control of adrenocortical function: a new role for the medulla? J Endocrinol 124:7–9

    Google Scholar 

  • Jones CT, Edwards AV (1990a) Release of adrenocorticotrophin from the adrenal gland in the conscious calf. J Physiol (Lond) 426:397–407

    Google Scholar 

  • Jones CT, Edwards AV (1990b) Adrenal responses to corticotrophin-releasing factor in conscious hypophysectomized calves. J Physiol (Lond) 430:25–36

    Google Scholar 

  • Jones CT, Edwards AV (1992) The role of corticotrophin-releasing factor in relation to the neural control of adrenal function in conscious calves. J Physiol (Lond) 447:489–500

    Google Scholar 

  • Kasprzak A, Rebuffat P, Meneghelli V, Mazzocchi G, Nussdorfer GG (1991) Prolonged interleukin-1β administration stimulates the growth of the rat adrenal zona fasciculata. Biomed Res 12:259–262

    Google Scholar 

  • Li CH, Chung D, Yamashiro D, Lee CY (1978) Isolation, characterization and synthesis of a corticotropin-inhibiting peptide from human pituitary glands. Proc Natl Acad Sci USA 75:4306–4309

    Google Scholar 

  • Mazzocchi G, Rebuffat P, Meneghelli V, Nussdorfer GG (1989) Effects of the infusion with AcTH or CRH on the secretory activity of rat adrenal cortex. J Steroid Biochem 32:841–843

    Google Scholar 

  • McCann SM (1991) Neuroregulatory peptides. In: Motta M (ed) Brain endocrinology. Raven Press, New York, pp 1–30

    Google Scholar 

  • Miller WL (1988) Molecular biology of steroid hormone synthesis. Endocr Rev 9:295–318

    Google Scholar 

  • Minamino H, Uehara A, Arimura A (1988) Biological and immunological characterization of corticotropin-releasing activity in the bovine adrenal medulla. Peptides 9:37–45

    Google Scholar 

  • Mrotek JJ, Mathew JK, Curtis JC, Johansson KP (1981) A method for the isolation of lipid droplet fractions from decapsulated rat adrenals. Steroids 38:229–241

    Google Scholar 

  • Müller OA, Werder K von (1991) Corticotropin-releasing hormone. In: Motta M (ed) Brain endocrinology. Raven Press, New York, pp 351–375

    Google Scholar 

  • Nussdorfer GG (1986) Cytophysiology of the adrenal cortex. Int Rev Cytol 98:1–405

    Google Scholar 

  • Nussdorfer GG, Mazzocchi G (1983) Long-term effects of ACTH on rat adrenocortical cells: a coupled stereological and enzymological study. J Steroid Biochem 19:1753–1756

    Google Scholar 

  • Nussdorfer GG, Malendowicz LK, Meneghelli V, Mazzocchi G (1992) Neurotensin enhances plasma adrenocorticotropin concentration by stimulating corticotropin-releasing hormone secretion. Life Sci 50:639–643

    Google Scholar 

  • Oers JWAM van, Tilders FJH (1991) Non-adrenocorticotropin mediated effects of endogenous corticotropin-releasing factor on the adrenocortical activity in the rat. J Neuroendocrinol 3:119–121

    Google Scholar 

  • Oers JWAM van, Hinson JP, Binnekade B, Tilders FJH (1992) Physiological role of corticotropin-releasing factor in the control of adrenocorticotropin-mediated corticosterone release from the rat adrenal gland. Endocrinology 130:282–288

    Google Scholar 

  • Palkovitz M, Fischer J (1968) Karyometric investigations. Akademiai Kiado, Budapest

    Google Scholar 

  • Rebuffat P, Kasprzak A, Andreis PG, Mazzocchi G, Gottardo G, Coi A, Nussdorfer GG (1989) Effects of prolonged cyclosporine-A treatment on the morphology and function of rat adrenal cortex. Endocrinology 125:1407–1413

    Google Scholar 

  • Rees LH, Cook DM, Kendall JW, Kramer RM, Ratcliffe JG, Knight RA (1971) A radioimmunoassay for rat plasma ACTH Endocrinology 89:254–261

    Google Scholar 

  • Rivier J, Rivier C, Vale W (1984) Synthetic competitive antagonist of corticotropin-releasing factor: effect on ACTH secretion in the rat. Science 224:889–890

    Google Scholar 

  • Saperstein A, Brand H, Audhya T, Nabriski D, Hutchinson B, Rosenzweig S, Hollander CS (1992) Interleukin-1β mediates stress-induced immunosuppression via corticotropin-releasing factor. Endocrinology 130:152–158

    Google Scholar 

  • Sapolsky R, Rivier C, Yamamoto G, Plotsky P, Vale W (1987) Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science 238:522–524

    Google Scholar 

  • Simpson ER, Waterman MR (1992) Regulation of expression of adrenocortical enzymes. In: James VHT (ed) The adrenal gland. Raven Press, New York, pp 191–208

    Google Scholar 

  • Sippell WG, Bidlingmaier F, Becker H, Brünig T, Dörr H, Hahn H, Golder W, Hollmann G, Knorr D (1978) Simultaneous radioimmunoassay of plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol and cortisone. J Steroid Biochem 9:63–74

    Google Scholar 

  • Suda T, Tomori N, Tozawa F, Mouri T, Demura H, Shizume K (1984) Distribution and characterization of immunoreactive corticotropin-releasing factor in human tissues. J Clin Endocrinol Metab 59:861–867

    Google Scholar 

  • Suda T, Tomori N, Yajima F, Odagini E, Demura H, Shizume K (1986) Characterization of immunoreactive corticotropin and corticotropin-releasing factor in human adrenal and ovarian tumors. Acta Endocrinol (Copenh) 111:546–552

    Google Scholar 

  • Suda T, Tozawa F, Ushiyama T, Sumitomo T, Yamada M, Demura H (1990) Interleukin-1 stimulates corticotropin-releasing factor gene expression in rat hypothalamus. Endocrinology 126:1223–1228

    Google Scholar 

  • Sweep CGJF, Meer MJM van der, Hermus ARMM, Smals AGH, Meer JWM van der, Pesman GJ, Willemsen SJ, Benraad TJ, Kloppenborg PWC (1992) Chronic stimulation of the pituitary-adrenal axis in rats by interleukin-1β infusion: in vivo and in vitro studies. Endocrinology 130:1153–1164

    Google Scholar 

  • Tsagarakis S, Gillies G, Rees LH, Besser M, Grossman A (1989) Interleukin-1 directly stimulates the release of corticotropin-releasing factor from rat hypothalamus. Neuroendocrinology 49:98–101

    Google Scholar 

  • Udelsman R, Harwood JP, Millan MA, Chrousos GP, Goldstein DS, Zimlichman R, Catt KJ, Aguilera G (1986) Functional corticotropin-releasing factor receptors in the primate peripheral sympathetic nervous system. Nature 319:147–150

    Google Scholar 

  • Uehara A, Gottschall PE, Dahl RR, Arimura A (1987) Interleukin-1 stimulates ACTH release by an indirect action which requires endogenous corticotropin-releasing factor. Endocrinology 121:1580–1582

    Google Scholar 

  • Weibel ER (1979) Stereological methods. 1. Practical methods for biological morphometry. Academic Press, London

    Google Scholar 

Download references

Author information

Author notes

  1. Anna Markowska

    Present address: Department of Histology and Embryology, School of Medicine, Swiecickiego 6, PL-60781, Poznan, Poland

Authors and Affiliations

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

    Anna Markowska, Piera Rebuffat, Stefano Rocco, Giuseppe Gottardo, Giuseppina Mazzocchi & Gastone G. Nussdorfer

Authors
  1. Anna Markowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Piera Rebuffat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefano Rocco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuseppe Gottardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giuseppina Mazzocchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gastone G. Nussdorfer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Markowska, A., Rebuffat, P., Rocco, S. et al. Evidence that an extrahypothalamic pituitary corticotropin-releasing hormone (CRH)/adrenocorticotropin (ACTH) system controls adrenal growth and secretion in rats. Cell Tissue Res 272, 439–445 (1993). https://doi.org/10.1007/BF00318550

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00318550

Key words

Search

Navigation