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Morphofunctional study of the effects of fetal exposure to cyproterone acetate on the hypothalamo-pituitary-gonadal axis of adult rats

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Summary

Fetal exposure to cyproterone acetate (CPA), while allowing, normal sexual morphogenesis, has previously been shown to lead to functional endocrine abnormalities in adult rats of both sexes. Because of this, we examined morphologically and morphometrically the hypothalamic nuclei involved in sexual dimorphism as well as the pituitary lactotropes of rats exposed in utero from day 15 to 20 of gestation to CPA. Male and female offspring was studied at the age of 70–80 days. In both sexes the brain weight was lower (p<0.05) in CPA-treated than in control rats. Morphometrical investigations showed that the surface density (Sv) and the volume density (Vv) of the ventromedial nucleus were higher (p<0.05) in CPA-treated male than in control rats. By comparing sexes the Sv and Vv of the ventromedial nucleus were higher (p<0.01) in CPA-treated male than in corresponding female rats. Also the nuclear surface of the tyrosine hydroxylase-immunoreactive neurons of the arcuate nucleus was higher (p<0.05) in CPA-treated male than in female rats. In lactotropes of the pituitary gland the immunoreactive prolactin (PRL) was densitometrically increased (p< 0.05) in CPA-treated female compared with control rats. By electron microscopy, PRL granules and autophagocytosis appeared to be more abundant in CPA-treated rats of both sexes. These data show that fetal exposure to CPA results in long-term anatomical and physiological alterations of hypothalamic and preoptic nuclei as well as of the pituitary lactotropes. These permanent changes support the functional endocrine abnormalities observed in adult rats.

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References

  • Agnati LF, Fuxe K, Zoli M, Zini I, Härfstrand A, Toffano G, Goldstein M (1988) Morphometrical and microdensitometrical studies on phenylethanolamine-N-methyltransferase-and neuropeptide Y-immunoreactive neurons in the rostral medulla oblongata of the adult and old male rat. Neuroscience 26:461–478

    Google Scholar 

  • Arnold AP, Gorski RA (1984) Gonadal steroid induction of structural sex differences in the central nervous system. Ann Rev Neurosci 7:413–442

    Google Scholar 

  • Brinkmann AO, Lindh LM, Breedveld DI, Mulder E, van der Molen HJ (1983) Cyproterone acetate prevents translocation of the androgen receptor in the rat prostate. Mol Cell Endocrinol 32:117–129

    Google Scholar 

  • Callaway TW, Bruchovsky N, Rennie PS, Comeau T (1982) Mechanisms of action of androgens and antiandrogens: Effects of antiandrogens on translocation of cytoplasmic androgen receptor and nuclear abundance of dihydrotestosterone. Prostate 3:599–610

    Google Scholar 

  • Childs GV, Lloyd JM, Unabia G, Gharib SD, Wierman ME, Chin WW (1987) Detection of luteinizing hormone B messenger ribonucleic acid (RNA) in individual gonadotropes after castration: use of a new in situ hybridization method with a photobiotinylated complementary RNA probe. Mol Endocrinol 1:926–932

    Google Scholar 

  • Döhler KD, Coquelin A, Davis F, Hines M, Shryne JE, Gorski RA (1982) Differentiation of the sexually dimorphic nucleus in the preoptic area of the rat brain is determined by the perinatal hormone environment. Neurosci Lett 33:295–298

    Google Scholar 

  • Döhler KD, Coquelin A, Davis F, Hines M, Shryne JE, Gorski RA (1984) Pre- and postnatal influence of testosterone proprionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats. Brain Res 302:291–295

    Google Scholar 

  • Gomez F, Monnier B, Lemarchand-Béraud T (1984) Foetal exposure to low doses of cyproterone acetate in the rat leads to functional endocrine abnormalities despite normal sexual morphogenensis. Acta Endocrinol 106:411–419

    Google Scholar 

  • Gorski RA, Gordon JH, Shryne JE, Southam AM (1978) Evidence for a morphological sex difference within the medial preoptic area of the rat brain. Brain Res 148:333–346

    Google Scholar 

  • Gorski RA, Jacobson CD (1982) Sexual differentiation of the brain. Front Horm Res 10:1–14

    Google Scholar 

  • Harlan RE, Gordon JH, Gorski RA (1979) Sexual differentiation of the brain: Implications for neuroscience. In: Schneider DM (ed) Review of Neuroscience 4. Raven Press, New York, pp 31–71

    Google Scholar 

  • Hines M, Davis FC, Coquelin A, Goy RW, Gorski RA (1985) Sexually dimorphic regions in the medial preoptic area and the bed nucleus of the stria terminalis of the guinea pig brain: A description and an investigation of their relationship to gonadal steroids in adulthood. J Neurosci 5:40–47

    Google Scholar 

  • Huang JK, Bartsch W, Voigt KD (1985) Interactions of an antiandrogen (cyproterone acetate) with the androgen receptor system and its biological action on the rat ventral prostate. Acta Endocrinol 109:569–576

    Google Scholar 

  • König JFR, Klippel RA (1974) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. RE Krieger, Huntington NY

    Google Scholar 

  • Lloyd JM, Childs GV (1988) Differential storage and release of luteinizing hormone and follicle-releasing hormone from individual gonadotropes separated by centrifugal elutriation. Endocrinology 122:1282–1290

    Google Scholar 

  • Matsumoto A, Arai Y (1980) Sexual dimorphism in wiring pattern in the hypothalamic arcuate nucleus and its modification by neonatal hormonal environment. Brain Res 190:238–242

    Google Scholar 

  • Matsumoto A, Arai Y (1983) Sex difference in volume of the ventromedial nucleus of the hypothalamus in the rat. Endocrinol Jpn 30:277–280

    Google Scholar 

  • Mittra I (1980) A novel “cleaved prolactin” in the rat pituitary: Part I. Biosynthesis, characterization and regulatory control. Biochem Biophys Res Comm 95:1750–1759

    Google Scholar 

  • Morin A, Rosenbaum E, Tixier-Vidai A (1984) Effects of thyrotropin-releasing hormone on prolactin compartments in normal rat pituitary cells in primary culture. Endocrinology 115:2278–2284

    Google Scholar 

  • Neumann F, von Berswordt-Wallrabe R, Elger W, Steinbeck H, Hahn JD, Kramer M (1970) Aspects of androgen-dependent events as studied by antiandrogens. Rec Prog Horm Res 26:337–410

    Google Scholar 

  • Oetting WS, Walker AM (1986) Differential isoform distribution between stored and secreted prolactin. Endocrinology 119:1377–1381

    Google Scholar 

  • Owens RE, Casanueva FF, Friesen HG (1985) Comparison between rat prolactin radioimmunoassay and bioassay values under different experimental and physiological conditions. Mol Cell Endocrinol 39:131–140

    Google Scholar 

  • Parsons B, Rainbow TC, McEwen BS (1984) Organizational effects of testosterone via aromatization on feminine reproductive behavior and neural progestin receptors in rat brain. Endocrinology 115:1412–1417

    Google Scholar 

  • Rossi GL, Probst D, Panerai AE, Cocchi D, Locatelli V, Müller EE (1979) Ultrastructure of somatotrophs of rats with median eminence lesions: Studies in basal conditions and after thyrotropin-releasing hormone stimulation. Neuroendocrinology 29:100–109

    Google Scholar 

  • Rossi GL, Bestetti G (1983) Technical aspects in the study of pathologic lesions in the hypothalamus of the rat. In: Jones TC, Mohr U, Hunt RD (eds) Endocrine system: monographs on pathology of laboratory animals. Springer, Berlin Heidelberg New York Tokyo, pp 311–316

    Google Scholar 

  • Shah GN, Hymer WC (1989) Prolactin variants in the rat adenohypophysis. Mol Cell Endocrinol 61:97–107

    Google Scholar 

  • Sinha YN, Gilligan TA (1981) Identification of a less immunoreactive form of prolactin in the rat pituitary. Endocrinology 108:1091–1094

    Google Scholar 

  • Tarttelin MF, Gorski RA (1988) Postnatal influence of diethylstilbestrol on the differentiation of the sexually dimorphic nucleus in the rat is as effective as perinatal treatment. Brain Res 456:271–274

    Google Scholar 

  • Traish AM, Muller RE, Wotiz HH (1985) Interaction of cyproterone acetate with rat prostatic androgen receptors. Steroids 45:247–262

    Google Scholar 

  • Wallis M, Daniels M, Ellis SA (1980) Size heterogeneity of rat pituitary prolactin. Biochem J 189:605–614

    Google Scholar 

  • Weinstein LA, Landis DMD, Sagar SM, Millard WJ, Martin JB (1984) Cysteamine depletes prolactin (PRL) but does not alter the structure of PRL-containing granules in the anterior pituitary. Endocrinology 115:1543–1550

    Google Scholar 

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Rossi, G.L., Bestetti, G.E., Reymond, M.J. et al. Morphofunctional study of the effects of fetal exposure to cyproterone acetate on the hypothalamo-pituitary-gonadal axis of adult rats. Exp Brain Res 83, 349–356 (1991). https://doi.org/10.1007/BF00231158

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  • DOI: https://doi.org/10.1007/BF00231158

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