Journal of Endocrinological Investigation

, Volume 12, Issue 4, pp 221–227 | Cite as

Effects of bromocriptine on pituitary and adrenal cortex in pre-adrenarchal rabbits

  • R. Pérez-Fernandez
  • F. Facchinetti
  • T. Garcia Caballero
  • A. R. Genazzani
  • J. Devesa


The effect of bromocriptine on the morphological picture and steroid content of the adrenal gland, and on certain pro-opiomelanocortin (C) peptides in the pituitary gland was evaluated in preadrenarchal rabbits. Eighteen immature male rabbits (5 weeks of age), were treated for 10 days with saline (n = 10, 2 ml sc) or bromocriptine mesylate (n = 8, 3 mg/kg sc) two times/day. After the last administration all animals received dexamethasone (0.25 mg im) and the next morning, 60 min after ACTH injection (0.25 mg im), plasma was drawn and they were sacrificed. Adrenals and pituitaries were immediately removed. For each animal, one adrenal gland was fixed, dehydrated and embedded in paraffin for histology; the other one was stored in saline for determination of androstenedione (A), dehydroepiandrosterone (DHA), 17-OH progesterone (17 P), and cortisol. Steroids were analyzed by RIA after previous extraction and celite-ethyleneglycol cromatography, or directly (cortisol). The immunoreactivities (ir) related to beta-Endorphin (B-EP), ACTH and alpha-MSH were evaluated in pituitary homogenates using speficic RIAs. The bromocriptine-treated rabbits showed a significant increase in the percentage of the adrenal zona reticularis (21.5 ± 3.9% of total cortex vs. 12.7 ± 1.3% in controls, p< 0.05, mean ± SE), and a decrease of the zona fasciculata (57.6 ± 3.13% vs. 67.7 ± 2.05% in controls, p < 0.05). No significant changes were observed in the relative percentage of the zona glomerulosa. While, after ACTH stimulation, the adrenal content of cortisol, 17 P and A was similar in both groups of animals, the A/17 P ratio, was significantly (p < 0.05) higher in treated (0.19 ± 0.02) than in control rabbits (0.10 ± 0.01). Given that the apparent efficiency of the combined activities of 11 beta and 21 hydroxylase appears to be the same in both groups (ratio cortisol × 103/17 P: 33.5 ± 5.7 vs 39.3 ± 6.5 in controls), bromocriptine-treated rabbits showed a clear predominance of androgenic over glucocorticoid responses, as demonstrated by the significant (p< 0.01 ) less ratio cortisol × 103/A in these animals (137.2 ±27.6) than in controls (318 ± 41.4). Bromocriptine-treated rabbits also showed significantly greater pituitary content of both ir alpha-MSH (2.01 ±0.47 pmol/mg) and ir B-EP (20.1 ± 4.0 fmol/mg) than controls (0.94 ± 0.23 pmol/mg, alpha-MSH, p < 0.05; 6.9 ± 1.96 fmol/mg, B-EP, p < 0.01). The pituitary ir ACTH was similar in both groups. In conclusion, these results indicate that bromocriptine treatment during the preadrenarchal period in rabbits: a) Induces the growth of the adrenal zona reticularis, which is accompanied by the increase of 17–20 desmolase activity, and b) Increases the pituitary content of alpha-MSH and B-EP ir. Taken together, these facts seem to indicate that adrenarche could occur as à phenomenon related to alpha-MSH and/or other factor(s) subject to dopaminergic control, but independent of ACTH.


Bromocriptine rabbit adrenarche zona reticularis POMC dopamine 


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  1. 1.
    Dhom G. The prepuberal and puberal growth of the adrenal (adrenarche). Beitr. Pathol. Bd. 150: 357, 1973.CrossRefGoogle Scholar
  2. 2.
    Genazzani A.R., Facchinetti F., Petraglia F., Pintor C., Bagnoli F, Puggioni R., Corda R. Correlations between plasma levels of opioid peptides and adrenal androgens in prepuberty and puberty. J. Steroid Biochem., 19: 891, 1983.PubMedCrossRefGoogle Scholar
  3. 3.
    Robba C., Rebuffat P., Mazocchi G., Nussdorfer G.G. Opposed effect of chronic prolactin administration on the zona fasciculata and zona reticularis of the adrenal cortex: an ultrastructural study. J. Submicroscop. Cytol. 17: 255, 1985.Google Scholar
  4. 4.
    Baird A., Kan K.N., Solomon S. Role of pro-opiomelanocortin-derived peptides in the regulation of steroid production by human fetal adrenal cells in culture. J. Endocrinol. 97: 357, 1979.CrossRefGoogle Scholar
  5. 5.
    Pérez-Fernandez R., Facchinetti F., Beiras A., Lima L., Juan Gaudiero G., Genazzani A.R., Devesa J. Morphological and functional stimulation of adrenal reticularis zone by dopaminergic blockade in dogs. J. Steroid. Biochem. 28: 465, 1987.PubMedCrossRefGoogle Scholar
  6. 6.
    Facchinetti F., Pérez-Fernandez R., Toma M.O., Gaudiero G.J., Lechuga M.J., Devesa J., Genazzani A.R. Dopamine acts on acetylation of propiomelanocortin-derived products in dog pituitary. Acta Endocrinol. (Copenh.) 117: 33, 1988.Google Scholar
  7. 7.
    Roaf R. A study of the adrenal cortex of the rabbit. J.Amat. 70: 126, 1935.Google Scholar
  8. 8.
    Cutler G.B., Gleen M., Bush M., Hodgen G.D., Graham C.E., Loriaux D.L. Adrenarche: A survey of rodents, domestic animals and primates. Endocrinology 103: 2112, 1978.PubMedCrossRefGoogle Scholar
  9. 9.
    Schiebinger R.J., Albertson B.D., Barnes K.M., Cutler G.B., Loriaux D.L. Development changes in rabbit and dog adrenal function: A possible homologue of adrenarche in the dog. Am. J. Physiol. 240: E693, 1981.Google Scholar
  10. 10.
    Schimchowitsch S., Palacios J.M., Stoeckel M.E., Schmitt G., Porte A. Absence of inhibitory dopaminergic control of the rabbit pituitary gland intermediate lobe. Neuroendocrinology 42: 71, 1986.PubMedCrossRefGoogle Scholar
  11. 11.
    Genazzani A.R., Inaudi P., D’Ambrogio G., Romagnino S., Nasi A., Facchinetti F. Plasma androgens and menstrual cycle: Physiopathological correlates from adolescence to menopause. Horm. Res. 18: 84, 1983.PubMedCrossRefGoogle Scholar
  12. 12.
    Abraham G.E. Radioimmunoassay of plasma steroid hormones. In: Huftmann E. (Ed.), Modern methods of steroid analysis. Academic Press, London, 1973, p. 451.Google Scholar
  13. 13.
    Carli G., Petraglia F., Facchinetti F., Cerri R., Genazzani A.R., Farabollini F, Lupo C. Opioids involvement in animal hypnosis in rabbits. In: Muller E.E., Genazzani A.R. (Eds.), Central and peripheral endorphins: basic and clinical aspects. Raven Press, New York, 1984, p. 133.Google Scholar
  14. 14.
    Genazzani A.R., Nappi G., Facchinetti F., Mazella G.L., Parrini E., Sinforiani E., Petraglia F., Savolidi F. Central deficiency of B-Endorphin in alcohol addicts. J. Clin. Endocrinol. Metab. 55: 583, 1982.PubMedCrossRefGoogle Scholar
  15. 15.
    Facchinetti F., Petraglia F., Nappi G., Martignoni E., Antoni G., Parrini D., Genazzani A.R. Different patterns of central and peripheral B-EP, B-LPH and ACTH throughout life. Peptides 4: 469, 1983.PubMedCrossRefGoogle Scholar
  16. 16.
    Hullinger R.L. Adrenal Cortex in the dog (Canis familiaris). I. Histomorphological changes during growth, maturity, and aging. Zentralbe. Veterinaermed. 7: 1, 1978.Google Scholar
  17. 17.
    Hooper B.R., Yen S.S.C. Circulating concentrations of dehydroepiandrosterone and dehydropiandrosterone sulphate during puberty. J. Clin. Endocrinol. Metab. 52: 1129, 1981.CrossRefGoogle Scholar
  18. 18.
    Rich B.H., Rosenfield R.L., Lucky A.W., Heike J.L., Otto P. Adrenarche: Changing adrenal response to adreno-corticotropin. J. Clin. Endocrinol. Metab. 52: 1129, 1981.PubMedCrossRefGoogle Scholar
  19. 19.
    Hornsby P.J. The regulation of adrenocortical function by control of growth and structure. In: Anderson D.C., Winter J.S.D. (Eds.), Adrenal cortex. Butterworths International Medical Reviews, London, 1985, p. 1.CrossRefGoogle Scholar
  20. 20.
    Shanker G., Sharma R.K. B-Endorphin stimulates corticosterone synthesis in isolated rat adrenal cells. Biochem. Biophys. Res. Comm. 86: 1, 1979.PubMedCrossRefGoogle Scholar
  21. 21.
    Robba C., Rebuffat P., Mazzocchi G., Nussdorfer G.G. Long-term trophic action of alpha-MSH on the zona glomerulosa of rat adrenal cortex. Acta Endocrinol. (Kbh.) 112: 404, 1984.Google Scholar
  22. 22.
    Estivariz F.E., Iturriza F.C., McLean C., Hope J., Lowry P.J. Stimulation of adrenal mitogenesis by N-terminal propiocortin peptides. Nature 297: 419, 1982.PubMedCrossRefGoogle Scholar
  23. 23.
    Challis J.R.G. Torosis J.D. Is MSH a trophic hormone to adrenal function in the foetus? Nature 269: 818, 1977.Google Scholar
  24. 24.
    Lowry P.J., McMartin C., Peters J. Properties of a simplified bioassay for adrenocorticotrophic activity using the steroidogenic response of isolated adrenal cells. J. Endocrinol. 59: 43, 1973.PubMedCrossRefGoogle Scholar
  25. 25.
    Devesa J., Pérez-Fernàndez R., Bokser L., Gaudiero G.J., Lima L., Casanueva F.F. Adrenal androgen secretion and dopaminergic activity in anorexia nervosa. Horm. Metab. Res. 20: 57, 1988.PubMedCrossRefGoogle Scholar
  26. 26.
    Tilders F.H.J., Smelik P.G. Direct neural control of MSH secretion in mammals. The involvement of dopaminergic tuberohypophyseal neurones. Front. Horm. Res. 4: 80, 1977.Google Scholar
  27. 27.
    Farah J.M., Malcom D.S., Mueller G.P. Dopaminergic inhibition of pituitary B-endorphin-like immunoreactivity secretion in rat. Endocrinology 110: 657, 1982.PubMedCrossRefGoogle Scholar
  28. 28.
    Smith A.I., Funder J.N. Proopiomelanocortin processing in the pituitary. Central nervous system, and peripheral tissues. Endocr. Rev. 9: 159, 1988.PubMedCrossRefGoogle Scholar
  29. 29.
    Orwoll E.S., Kendall J.W. B-Endorphin and adrenocorticotropin in extrapituitary sites: Gastrointestinal tract. Endocrinology 107: 438, 1980.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1989

Authors and Affiliations

  • R. Pérez-Fernandez
    • 1
  • F. Facchinetti
    • 3
  • T. Garcia Caballero
    • 2
  • A. R. Genazzani
    • 3
  • J. Devesa
    • 1
  1. 1.Spain
  2. 2.School of MedicineUniversity of Santiago de CompostelaSpain
  3. 3.Dept. of Obstetrics and Gynecology, School of MedicineUniversity of ModenaItaly

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