Skip to main content
SpringerLink
Log in

Short- and long-term effects of ACTH on the adrenal zona glomerulosa of the rat

A coupled stereological and enzymological study

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

Summary

Short-term ACTH treatment provoked a decrease in volume of the lipid-droplet compartment in rat zona glomerulosa cells, and a rise in plasma and intracellular concentrations of corticosterone and aldosterone. It enhanced activities of 3β-hydroxysteroid dehydrogenase (3βHSD), 11β-hydroxylase (11βOH) and 18-hydroxylase (18OH). Long-term ACTH administration produced a hypertrophy of the zona glomerulosa and its parenchymal cells, a result of the increase in volume of the smooth endoplasmic reticulum and the mitochondrial compartment. The surface area per cell of mitochondrial inner membranes increased; the tubular cristae were transformed into a homogeneous population of vesicles. The plasma and intracellular concentrations of corticosterone further increased, whereas those of aldosterone fell below basal levels (the “aldosterone-escape” phenomenon). The activities of 3βHSD and 11βOH were enhanced, that of 180H decreased. Therefore, ACTH stimulates zona glomerulosa growth and transforms parenchymal elements into zona fasciculata celltypes. Cyanoketone nullified acute ACTH effects on plasma and intracellular concentrations of corticosterone and aldosterone, but did not affect the activities of 11βOH and 18OH. Chronic ACTH treatment produced similar results, although 18OH activity was not suppressed. The mechanism underlying the “aldosterone-escape” phenomenon may thus involve a rise in the intracellular concentration of corticosterone, caused by the enhanced synthesis and activation of 3βHSD and 11βOH.

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, Catt KJ (1979) Loci of action of regulators of aldoster-one biosynthesis in isolated glomerulosa cells. Endocrinology 104:1046–1052

    Google Scholar 

  • Aguilera G, Menard RH, Catt KJ (1980) Regulatory actions of angiotensin II on receptors and steroidogenic enzymes in adrenal glomerulosa cells. Endocrinology 107:55–60

    Google Scholar 

  • Aguilera G, Fujita K, Catt KJ (1981) Mechanisms of inhibition of aldosterone secretion by adrenocorticotropin. Endocrinology 108:522–528

    Google Scholar 

  • Armato U, Nussdorfer GG, Andreis PG, Mazzocchi G, Draghi E (1974) Primary tissue culture of human adult adrenocortical cells. Methodology and electron microscopic observations on ACTH-deprived and ACTH-treated cortical cells. Cell Tissue Res 155:155–180

    Google Scholar 

  • Balasubramaniam S, Goldstein JL, Faust JR, Brunschede GY, Brown MS (1979) Lipoprotein-mediated regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesteryl ester metabolism in the adrenal gland of the rat. J Biol Chem 252:1771–1779

    Google Scholar 

  • Baniukiewicz S, Brodie A, Flood C, Motta M, Okamoto M, Tait JF, Tait SAS, Blair-West JR, Coghlan JP, Denton DA, Goding JR, Scoggins BA, Wintour AM, Wright RD (1968) Adrenal biosynthesis of steroids in vivo and in vitro using continuous superfusion and infusion procedures. In: McKerns KW (ed) Functions of the adrenal cortex. North Holland Publishing Company, Amsterdam, pp 153–232

    Google Scholar 

  • Basch RS, Finegold MJ (1971) 3β-hydroxysteroid dehydrogenase activity in the mitochondria of rat adrenal homogenates. Biochem J 125:983–989

    Google Scholar 

  • Baumann K, Müller J (1974) Effects of hypophysectomy with or without ACTH maintenance therapy on the final steps of aldosterone biosynthesis in the rat. Acta Endocrinol 76:102–116

    Google Scholar 

  • Bliss CI (1967) Statistics in biology. Vol 1. MacGraw-Hill, New York

    Google Scholar 

  • Boyd GS, McNamara B, Suckling KE, Tocher DR (1983) Cholesterol metabolism in the adrenal cortex. J Steroid Biochem 19:1017–1027

    Google Scholar 

  • Carr BR, Simpson ER (1981) Lipoprotein utilization and cholesterol synthesis by the human fetal adrenal gland. Endocr Rev 2:306–326

    Google Scholar 

  • Carr BR, Ohashi M, Simpson ER (1982) Low density lipoprotein binding and de novo synthesis of cholesterol in the neocortex and fetal zones of the human fetal adrenal gland. Endocrinology 110:1994–1998

    Google Scholar 

  • Carsia RV, Malamed S (1979) Acute self-suppression of corticosteroidogenesis in isolated adrenocortical cells. Endocrinology 105:911–914

    Google Scholar 

  • Carsia RV, Malamed S (1983) Glucocorticoid control of steroidogenesis in isolated rat adrenocortical cells. Biochim Biophys Acta 763:83–89

    Google Scholar 

  • Dubois RN, Simpson ER, Kramer RE, Waterman MR (1981) Induction of synthesis of cholesterol side chain cleavage cytochrome-P450 by adrenocorticotropin in cultured bovine adrenocortical cells. J Biol Chem 256:7000–7005

    Google Scholar 

  • Frühling J, Sand G, Penasse W, Pecheux F, Claude A (1973) Corrélation entre la morphologie et le contenu lipidique des corticosurrénales du cobaye, du rat et du boeuf. J Ultrastruct Res 44:113–133

    Google Scholar 

  • Glàz E, Vecsei P (1971) Aldosterone. Pergamon Press, Oxford

    Google Scholar 

  • Gwynne JT, Hess B (1980) The role of high density lipoproteins in rat adrenal cholesterol metabolism and steroidogenesis. J Biol Chem 255:10875–10883

    Google Scholar 

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

    Google Scholar 

  • Hornsby PJ, Crivello JF (1983) The role of lipid peroxidation and biological antioxidants in the function of the adrenal cortex. Part 2. Mol Cell Endocrinol 30:123–147

    Google Scholar 

  • Hornsby PJ, O'Hare MJ (1977) The roles of potassium and corticosteroids in determining the pattern of metabolism of (3H)deoxy-corticosterone by monolayer cultures of rat adrenal glomerulosa cells. Endocrinology 101:997–1005

    Google Scholar 

  • Jungmann E, Magnet W, Rottmann-Kuhnke U, Sprey R, Schwedes U, Usadel KH, Schöffling K (1982) The inhibiting effect of trilostane on adrenal steroid synthesis: hormonal and morphological alterations induced by subchronic trilostane treatment in normal rats. Res Exp Med 180:193–200

    Google Scholar 

  • Kahri AI, Voutilainen R, Salmenperä M (1979) Different biological action of corticosteroids, corticosterone and Cortisol, as a base of zonal function of adrenal cortex. Acta Endocrinol 91:329–337

    Google Scholar 

  • Karnovsky MJ (1961) Simple method for staining with lead at high pH in electron microscopy. J Biophys Biochem Cytol 11:729–732

    Google Scholar 

  • Komor J, Müller J (1979) Effects of prolonged infusions of potassium chloride, adrenocorticotrophin or angiotensin II upon serum aldosterone concentration and the conversion of corticosterone to aldosterone in rats. Acta Endocrinol 90:680–691

    Google Scholar 

  • Kraiem Z, Rosenthal T, Rotzak R, Lunenfeld B (1979) Angiotensin II and K challenge following prolonged ACTH administration to normal subjects. Acta Endocrinol 91:657–665

    Google Scholar 

  • Kramer RE, Gallant S, Brownie AC (1979) The role of cytochrome P450 in the action of sodium depletion on aldosterone biosynthesis in rats. J Biol Chem 254:3953–3958

    Google Scholar 

  • Kramer RE, Gallant S, Brownie AC (1980) Actions of angiotensin II on aldosterone biosynthesis in the rat adrenal cortex. Effects on cytochrome P450 enzymes of the early and late pathway. J Biol Chem 255:3442–3447

    Google Scholar 

  • Legros F, Lehoux JG (1983) Changes in characteristics of rat adrenal glomerulosa cells under acute and chronic treatment with ACTH. Can J Biochem Cell Biol 61:538–546

    Google Scholar 

  • Lehoux JG, Lefebvre A (1981) The effect of ACTH on HMG-CoA reductase activity in hamster adrenals. Life Sci 29:1913–1919

    Google Scholar 

  • Loud AV (1962) A method for the quantitative estimation of cytoplasmic structures. J Cell Biol 15:481–487

    Google Scholar 

  • Marusić ET, Lobo MV, Foster R, White A (1982) Mécanismos de control de secrecion de corticoides: desarollo de un modelo experimental endocrinologico para estudios simultaneos a nivel celular y del organismo vivo. Arch Biol Med Exp (Santiago) 15:331–338

    Google Scholar 

  • McDougall JG, Butkus A, Coghlan JP, Denton DA, Müller J, Oddie CJ, Robinson PM, Scoggins BA (1980) Biosynthetic and morphological evidence for inhibition of aldosterone production following administration of ACTH to sheep. Acta Endocrinol 94:559–570

    Google Scholar 

  • Meuli C, Müller J (1982) Potassium intake and aldosterone biosynthesis: the role of cytochrome P-450. J Steroid Biochem 18:167–171

    Google Scholar 

  • Moses HL, Davis WW, Rosenthal AS, Garren LD (1969) Adrenal cholesterol: localization by electron-microscope autoradiography. Science 163:1203–1205

    Google Scholar 

  • Müller J (1971) Regulation of aldosterone biosynthesis. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Müller J (1978) Suppression of aldosterone biosynthesis by treatment of rats with adrenocorticotropin: comparison with glucocorticoid effect. Endocrinology 103:2061–2068

    Google Scholar 

  • Müller J, Baumann K (1974) Multifactorial regulation of the final steps of aldosterone biosynthesis in the rat. J Steroid Biochem 5:795–800

    Google Scholar 

  • Neri G, Gambino AM, Mazzocchi G, Nussdorfer GG (1978) Effects of chronic treatment with ACTH on the intracellular levels of cyclic-AMP and cyclic-GMP in the rat adrenal cortex. Experientia 34:815–816

    Google Scholar 

  • Neville AM, O'Hare MJ (1979) Aspects of structure, function and pathology. In: James VTH (ed) The adrenal gland. Raven Press, New York, pp 1–65

    Google Scholar 

  • Nussdorfer GG (1970) Effects of corticosteroid hormones on the smooth endoplasmic reticulum of the rat adrenocortical cells. Z Zellforsch 106:143–154

    Google Scholar 

  • Nussdorfer GG (1980) Cytophysiology of the adrenal zona glomerulosa. Int Rev Cytol 64:307–369

    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, Mazzocchi G, Rebuffat P (1973) An ultrastructural stereologic study of the effects of ACTH and adenosine 3′–5′-cyclic monophosphate on the zona glomerulosa of rat adrenal cortex. Endocrinology 92:141–151

    Google Scholar 

  • Nussdorfer GG, Mazzocchi G, Robba C, Belloni AS, Rebuffat P (1977) Effects of ACTH and dexamethasone on the zona glomerulosa of the rat adrenal cortex: an ultrastructural stereologic study. Acta Endocrinol 85:608–614

    Google Scholar 

  • Nussdorfer GG, Mazzocchi G, Meneghelli V (1978) Cytophysiology of the adrenal zona fasciculata. Int Rev Cytol 55:291–365

    Google Scholar 

  • Nussdorfer GG, Neri G, Belloni AS, Mazzocchi G, Rebuffat P, Robba C (1982) Effects of ACTH on the zona glomerulosa of sodium-loaded timolol maleate treated rats: stereology and plasma hormone concentrations. Acta Endocrinol 99:256–262

    Google Scholar 

  • Nussdorfer GG, Mazzocchi G, Rebuffat P, Malendowicz LK, Robba C (in preparation) Short- and long-term effects of angio-tensin II on the rat adrenal zona glomerulosa: a coupled stereological and enzymological study

  • Péron FG, McCarthy JL (1968) Corticosteroidogenesis in the rat adrenal gland. In: McKerns KW (ed) Functions of the adrenal cortex. North Holland Publishing Company, Amsterdam, pp 261–337

    Google Scholar 

  • Pham-Huu-Trung MT, de Smitter N, Bogyo A, Girard F (1984) Inhibition of cortisol production in isolated guinea pig adrenal cells. J Steroid Biochem 21:93–99

    Google Scholar 

  • Rybak SM, Ramachandran J (1982) Mechanism of induction of Δ5-3β-hydroxysteroid dehydrogenase isomerase activity in rat adrenocortical cells by corticotropin. Endocrinology 111:427–433

    Google Scholar 

  • Salomon DS, Sherman MI (1976) Gonadotrophin stimulation of progesterone synthesis by midpregnancy mouse ovarian cells in vitro. Endocrinology 99:800–808

    Google Scholar 

  • Sharawy M, Dirksen T, Chaffin J (1979) Increase in free cholesterol content of the adrenal cortex after stress: radioautographic and biochemical study. Am J Anat 156:567–576

    Google Scholar 

  • Sippell WG, Bidlingmaier F, Becker H, Brünig T, Dörr H, Golder W, Holmann 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 

  • Spät A, Jozan S (1972) Competitive protein binding assay of corti-costerone. J Steroid Biochem 3:755–759

    Google Scholar 

  • Tait JF, Tait SAS, Bell JBG, Hyatt PJ, Williams BC (1980) Further studies on the stimulation of rat adrenal capsular cells: four types of response. J Endocrinol 87:11–27

    Google Scholar 

  • Tamaoki BI (1973) Steroidogenesis and cell structure. Biochemical pursuit of sites of steroid synthesis. J Steroid Biochem 4:89–118

    Google Scholar 

  • Weibel ER, Bolender RP (1973) Stereological techniques for electron microscopic morphometry. In: Hayat MA (ed) Principles and techniques of electron microscopy, Vol 3. Van Nostrand Reinhold Company, New York, pp 237–296

    Google Scholar 

  • Weibel ER, Paumgartner D (1978) Integrated stereological and biochemical studies on hepatocytic membranes. II. Correlation of section thickness effect on volume and surface density estimates. J Cell Biol 77:584–597

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, University of Padua, Padua, Italy

    Giuseppina Mazzocchi, Ludwig K. Malendowicz, Piera Rebuffat, Claudia Robba, Giuseppe Gottardo &  Gastone G. Nussdorfer

  2. Department of Histology and Embryology, Academy of Medicine, Poznań, Poland

    Ludwig K. Malendowicz

Authors
  1. Giuseppina Mazzocchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ludwig K. Malendowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Piera Rebuffat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudia Robba
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giuseppe Gottardo
    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

Mazzocchi, G., Malendowicz, L.K., Rebuffat, P. et al. Short- and long-term effects of ACTH on the adrenal zona glomerulosa of the rat. Cell Tissue Res. 243, 303–310 (1986). https://doi.org/10.1007/BF00251044

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00251044

Key words

Search

Navigation