Skip to main content
SpringerLink
Log in
Book cover

Spermatogenesis — Fertilization — Contraception pp 123–141Cite as

Androgens and the Brain: Role of Testosterone Metabolism

  • Conference paper

  • 126 Accesses

Part of the book series: Schering Foundation Workshop ((SCHERING FOUND,volume 4))

Abstract

There is no doubt that the central nervous system (CNS) is an important target for practically all hormonal steroids; specific receptors for androgens, estrogens, progesterone, and corticoids have been shown to be present in several brain regions (Martini 1978). The CNS also represents an area of intense metabolism of steroid hormones. The study of the metabolism of androgens, and especially of testosterone, has been the subject of particularly active research; however, some studies have also been devoted to analyzing the metabolism of estrogen, progesterone and corticoids (Martini 1982). Moreover, it has recently been shown that the brain is also able to synthesize dehydroepiandrosterone, delta-5-pregnenolone and their respective sulfates (Baulieu and Robel 1990). All these observations underline that, at present, the brain must be viewed not only as an important target for steroid effects, but also as a structure which possesses the machinery for synthesizing hormone precursors and for metabolizing both these precursors and hormones originating in the peripheral steroidogenetic glands, in order to fulfill specific functional requirements.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anderson S, Berman DM, Jenkins EP, Russell DW (1991) Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism. Nature 354:159-161

    Google Scholar 

  • Baulieu E-E, Robel P (1990) Neurosteroids: a new brain function? J Steroid Biochem Molec Biol 37:395-403

    Google Scholar 

  • Bonsall RW, Zumpe D, Michael RP (1990) Comparisons of the nuclear uptake of (3H)-testosterone and its metabolites by the brains of male and female macaque fetuses at 122 days of gestation. Neuroendocrinology 51: 474–480

    Article  PubMed  CAS  Google Scholar 

  • Callard GV (1981) Aromatization is cyclic AMP-dependent in cultured brain cells. Brain Res 204: 461–464

    Article  PubMed  CAS  Google Scholar 

  • Campbell JS, Karavolas HJ (1989) The kinetic mechanism of the hypothalamic progesterone 5α-reductase. J Steroid Biochem 32: 283–289

    Article  PubMed  CAS  Google Scholar 

  • Canick JA, Vaccaro DE, Livingston EM, Leeman SE, Ryan KJ, Fox TO (1986) Localization of aromatase and 5α-reductase to neuronal and non-neuronal cells in the fetal rat hypothalamus. Brain Res 372: 277–282

    Article  PubMed  CAS  Google Scholar 

  • Celotti F, Negri-Cesi P, Limonta P, Melcangi C (1983) Is the 5α-reductase of the hypothalamus and of the anterior pituitary neurally regulated? Effects of hypothalamic deafferentiations and of centrally acting drugs. J Steroid Biochem 19: 229–234

    Article  PubMed  CAS  Google Scholar 

  • Celotti F, Maggi R, Melcangi RC, Negri-Cesi P, Martini L (1984) Metabolism of androgens in the rat and hamster neuroendocrine structures. In: Labrie F, Proulx L (eds) Endocrinology, Proceedings of the 7th International Congress of Endocrinology,Quebec City,1-7 July 1984, International Congress Series 655. Excerpta Medica, Amsterdam, pp 305–309

    Google Scholar 

  • Celotti F, Melcangi RC, Negri-Cesi P, Ballabio M, Martini L (1986) A comparative study of the metabolism of testosterone in the neuroendocrine structures of several animal species. Neuroendocrinol Lett 8: 227–235

    CAS  Google Scholar 

  • Celotti F, Melcangi RC, Negri-Cesi P, Ballabio M, Martini L (1987) Differential distribution of the 5α-reductase in the central nervous system of the rat and the mouse: are the white matter structures of the brain target tissue for testosterone action? J steroid Biochem 6: 125–129

    Article  Google Scholar 

  • Celotti F, Melcangi RC, Negri-Cesi P, Poletti A (1991) Testosterone metabolism in brain cells and membranes. J Steroid Biochem Molec Biol 40: 673–678

    Article  PubMed  CAS  Google Scholar 

  • Celotti F, Melcangi RC, Martini L (1992) The 5α-reductase in the brain: molecular apects and relation to brain function. Frontiers in Neuroendocrinol 13: 95–148

    Google Scholar 

  • Connolly PB, Resko JA (1989) Role of steroid 5α-reductase activity in sexual differentiation of the guinea pig. Neuroendocrinology 49: 324–330

    Article  PubMed  CAS  Google Scholar 

  • Connolly PB, Roselli CE, Resko JA (1990) Aromatase activity in adult guinea pig brain is androgen dependent. Biol. Reprod. 43: 698-703

    Google Scholar 

  • Davidson T, Tobin AM, Payne AP (1990) Maintenance of the spinal nucleus of bulbocavernosus and perineal muscles in female albino swiss rats treated with perinatal dihydrotestosterone. J Reprod Fert 90: 619–623

    Article  CAS  Google Scholar 

  • Frankfurt M, Gould E, Woolley CS, McEwen BS (1990) Gonadal steroids modify dendritic spine density in ventromedial hypothalamic neurons: A Golgi study in the adult rat. Neuroendocrinology 51: 530-535

    Google Scholar 

  • George FW, Peterson KG (1988) 5α-dihydrotestosterone formation is necess- ary for embryogenesis of the rat prostate. Endocrinology 122: 1159–1164

    Google Scholar 

  • Goldman JE, Abramson B (1990) Cyclic AMP-induced shape changes of astrocytes are accompanied by rapid depolymerization of actin. Brain Res 528: 189–196

    Article  PubMed  CAS  Google Scholar 

  • Halasz B, Pupp L (1965) Hormone secretion of the anterior pituitary gland after physical interruption of all nervous pathways to the hypophysiotropic area. Endocrinology 77: 553–562

    Article  PubMed  CAS  Google Scholar 

  • Hansson E (1989) Co-existence between receptors, carriers, and second messengers on astrocytes grown in primary cultures. Neurochemical Res14: 811819

    Google Scholar 

  • Hanukoglu I, Karavolas H J, Goy RW (1977) Progesterone metabolism in the pineal, brain stem, thalamus and corpus callosum of the female rat. Brain Res 125: 313–324

    Article  PubMed  CAS  Google Scholar 

  • Hutchison JB, Schumacher M, Hutchison RE (1990) Developmental sex differences in brain aromatase activity are related to androgen level. Dev Brain Res. 57: 187–195

    Article  CAS  Google Scholar 

  • Imperato-McGinley J, Shackleton C, Orlic S, Stoner E (1990) C19 and C21 513/5α metabolite ratios in subjects treated with the 5α-reductase inhibitor Finasteride: comparison of male pseudohermaphrodites with inherited 5αreductase deficiency. J Clin Endocrinol Metab 70: 777–78

    Article  PubMed  CAS  Google Scholar 

  • Jung-Testas I, Hu ZY, Baulieu EE, Robel P (1989) Neurosteroids: biosynthesis of pregnenolone and progesterone in primary cultures of rat glial cells. Endocrinology125: 2083–2091

    Google Scholar 

  • Kraulis I, Foldes G, Traikov H, Dubrovsky B, Birmingham MK Distribution, metabolism and biological activity of deoxycorticosterone in the central nervous system. Brain Res 88: 1–14

    Google Scholar 

  • Krieger NR, Scott RG, Jurman ME (1983) Testosterone 5α-reductase in rat brain. J Neurochem 40: 1460–1464

    Article  PubMed  CAS  Google Scholar 

  • Langub MC, Watson RE (1992) Estrogen receptor-immunoreactive glia, endothelia, and ependyma in guinea pig preoptic area and median eminence: electron microscopy. Endocrinology 130: 364–372

    Article  PubMed  CAS  Google Scholar 

  • Leedy M, Beattie MS, Bresnahan JC (1987) Testosterone-induced plasticity of sinaptic inputs to adult mammalian motoneurons. Brain Res 424: 386–390

    Article  PubMed  CAS  Google Scholar 

  • MacLusky NJ, Clark CR, Shanabrough M, Naftolin F (1987) Metabolism and binding of androgen in the spinal cord of the rat. Brain Res 422: 83–91

    Article  PubMed  CAS  Google Scholar 

  • Martini L (1978) The hypothalamus as an endocrine target organ. In: Cox B, Morris ID, Weston AH (eds) Pharmacology of the hypothalamus. MacMillan, London pp 227–245

    Google Scholar 

  • Martini L, Celotti F, Serio M (1979) 5α-reductase deficiency in humans: support to the theory that 5α-reduction of testosterone is an essential step in the control of LH secretion. J Endocrinol Invest 2: 463–464

    Google Scholar 

  • Martini L (1982) The 5α-reductase of testosterone in the neuroendocrine structures. Biochemical and physiological implications. Endocr Rev 3: 1–25

    Article  PubMed  CAS  Google Scholar 

  • Massa R, Martini L (1971/1972) Interference with the 5α-reductase system. A new approach for developing antiandrogens. Gynec Invest 2: 253–270

    Google Scholar 

  • Massa R, Justo S, Martini L (1975) Conversion of testosterone into 5α-reduced metabolites in the anterior pituitary and in the brain of maturing rats. J. Steroid Biochem. 6: 567–571

    Article  PubMed  CAS  Google Scholar 

  • Melcangi RC, Celotti F, Negri-Cesi P, Martini L (1985) Testosterone 5αlphareductase in discrete hypothalamic nuclear areas in the rat: effect of castration. Steroids 45: 347–356

    Article  PubMed  CAS  Google Scholar 

  • Melcangi RC, Celotti F, Poletti A, Negri-Cesi P, Martini L (1987) The 5α-reductase activity of the subcortical white matter, the cerebral cortex, and the hypothalamus of the rat and of the mouse: possible sex differences and effect of castration. Steroids 49: 259–270

    Article  PubMed  CAS  Google Scholar 

  • Melcangi RC, Celotti F, Ballabio M, Castano P, Poletti A, Milani S, Martini L (1988a) Ontogenetic development of the 5α-reductase in the rat brain: cerebral cortex, hypothalamus, purified myelin and isolated oligodendrocytes. Dey Brain Res 44: 181–188

    Article  CAS  Google Scholar 

  • Melcangi RC, Celotti F, Ballabio M, Poletti A, Castano P, Martini L (1988b) Testosterone 5α-reductase activity in the rat brain is higly concentrated in white matter structures and in purified myelin sheaths of axon. J. Steroid Biochem. 31: 173–179

    Article  PubMed  CAS  Google Scholar 

  • Melcangi RC, Celotti F, Ballabio M, Castano P, Massarelli R, Poletti A, Martini L (1990a) 5α-reductase activity in isolated and cultured neuronal and glial cells of the rat. Brain Res. 516: 229–236

    Google Scholar 

  • Melcangi RC, Celotti F, Ballabio M, Poletti A, Martini L(1990b) Testosterone metabolism in peripheral nerves: presence of the 5α-reductase-3a-hydroxysteroid-dehydrogenase enzymatic system in the sciatic nerve of adult and aged rats. J Steroid Biochem 35: 145–148

    Google Scholar 

  • Melcangi RC, Celotti F, Negri-Cesi P, Castano P, Massarelli R, Poletti A, Martini L (1990c) 5α-reductase and aromatase activity in isolated and cultured neuronal and glial cells of the rat. Program 72nd Meet Endocrine Soc Atlanta Abstract 1288

    Google Scholar 

  • Meyer JS (1985) Biochemical effects of corticosteroids on neuronal tissues. Physiol Rev 65: 946–1020

    PubMed  CAS  Google Scholar 

  • Motta M, Zoppi S, Martini L (1986) In vitro metabolism of testerone in the rat prostate: influence of aging. J Steroid Biochem 25: 897–903

    Article  PubMed  CAS  Google Scholar 

  • Naftolin F, Garcia-Segura LM, Keefe D, Leranth C, MacLusky NJ, Brawer JR (1990) Estrogen effects on the synaptology and neural membranes of the rat hypothalamic arcuate nucleus. Biol Reprod 42: 21–28

    Article  PubMed  CAS  Google Scholar 

  • Negri-Cesi P, Celotti F, Martini L (1989) Androgen metabolism in the male hamster. II. Aromatization of androstenadiol in the hypothalamus and in the cerebral cortex: kinetic parameters and effect of exposure to different photoperiods. J Steroid Biochem 32: 65–70

    Article  PubMed  CAS  Google Scholar 

  • Olmos G, Aguilera P, Tranque P, Naftolin F, Garcia-Segura LM (1987) Estrogen-induced synaptic remodelling in adult rat brain is accompanied by the reorganization of neuronal membranes. Brain Res 425: 57–64

    Article  PubMed  CAS  Google Scholar 

  • Ovaida H, Vlodaysky I, Abramsky O, Weidenfeld J (1984) Binding of hormonal steroids to isolated oligodendroglia and astroglia grown “in vitro” on a naturally produced extracellular matrix. Clin Neuropharmacol 7: 307–311

    Article  Google Scholar 

  • Palkovits M (1973) Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res 59: 449–450

    Article  PubMed  CAS  Google Scholar 

  • Perez J, Naftolin F, Garcia-Segura LM (1990) Sexual differentiation of synaptic connectivity and neuronal plasma membrane in the arcuate nucleus of the rat hypothalamus. Brain Res 527: 116–122

    Article  PubMed  CAS  Google Scholar 

  • Poletti A, Celotti F, Melcangi RC, Ballabio M, Martini L (1990) Kinetic properties of the 5α-reductase of testosterone in the purified myelin, in the subcortical white matter and in the cerebral cortex of the male rat brain. J Steroid Biochem 35: 97–101

    Article  PubMed  CAS  Google Scholar 

  • Roselli CE, Salisbury RL, Resko JA (1987a) Genetic evidence for androgen-dependent and independent control of aromatase activity in the rat brain. Endocrinology 121: 2205–2210

    Article  PubMed  CAS  Google Scholar 

  • Roselli CE, Stadelman H, Horton LE, Resko JA (1987b) Regulation of androgen metabolism and luteinizing hormone-releasing content in discrete hypothalamic and limbic areas of male rhesus macaques. Endocrinology 120: 97–106

    Article  PubMed  CAS  Google Scholar 

  • Sar M, Stumpf WE (1975) Distribution of androgen-concentrating neurons in rat brain. In: Stumpf WE, Grant LD (eds) Anatomical Neuroendocrinology. Karger, Basel pp 120–133

    Google Scholar 

  • Seil FJ, Blank NK, Leiman AL (1979) Toxic effects of kainic acid on mouse cerebellum in tissue culture. Brain Res 161: 253–265

    Article  PubMed  CAS  Google Scholar 

  • Selmanoff MK, Brodkin LD, Weiner RI, Siiteri PK (1977) Aromatization and 5α-reduction of androgens in discrete hypothalamic and limbic regions of the male and female rat. Endocrinology 101: 841–848

    Article  PubMed  CAS  Google Scholar 

  • Sheridan PJ (1984) Autoradiographic localization of steroid receptors in the brain. Clin. Neuropharmacol 7: 281–295

    Article  PubMed  CAS  Google Scholar 

  • Shima H, Tsuji M, Young P, Cunha GR (1990) Postnatal growth of mouse seminal vesicle is dependent on 5α-dihydrotestosterone. Endocrinology 127: 3222–3233

    Article  PubMed  CAS  Google Scholar 

  • Sholl SA, Goy RW, Kim KL (1989) 5α-Reductase, aromatase, and androgen receptor levels in the monkey brain during fetal development. Endocrinology 124: 627–634

    Google Scholar 

  • Snipes CA, Shore LS (1982) Metabolism of testosterone in vitro by hypothalamus and other areas of rat brain. Andrologia 14: 81–85

    Article  PubMed  CAS  Google Scholar 

  • Steimer T, Hutchison JB (1989) Is the androgen-dependent increase in preoptic estradiol-17b formation due to aromatase induction? Brain Res 480: 335–339

    Article  PubMed  CAS  Google Scholar 

  • Stumpf WE, Sar M (1975) Anatomical distribution of corticosterone-concentrating neurons in rat brain. In: Stumpf WE, Grant LD (eds) Anatomical Neuroendocrinology. Karger, Basel pp 254–261

    Google Scholar 

  • Stupnicka E, Massa R, Zanisi M, Martini L (1977) Role of the anterior pituitary and hypothalamic metabolism of progesterone in the control of gonadotropin secretion. Prog Reprod Biol 2: 88–95

    CAS  Google Scholar 

  • Weidenfeld J, Schorr J, Abramsky 0 (1982) Metabolism of gonadal steroids by oligodendrocytes of calf and rat brain. Program of 12th Annual Meeting of the Society for Neuroscience. Minneapolis, Minnesota. No. 63. 19

    Google Scholar 

  • Weidenfeld J, Abramsky 0, Ovadia H (1984) Metabolism of gonadal steroids by normal and neoplastic glial cells. Program of the 7th International Congress of Endocrinology. Quebec City. Excerpta Medica, Amsterdam No. 2745

    Google Scholar 

  • Zanisi M, Martini L (1979) Interaction of oestrogen and of physiological progesterone metabolites in the control of gonadotropin secretion. J Steroid Biochem 11: 855–862

    Article  PubMed  CAS  Google Scholar 

  • Zanisi M, Motta M, Martini L (1973) Inhibitory effect of the 5α-reduced meta- bolites of testosterone on gonadotrophin secretion. J Endocr 56: 315–316

    Article  PubMed  CAS  Google Scholar 

  • Zoppi S, Cocconi M, Lechuga MJ, Messi E, Zanisi M, Motta M (1988) Antihormonal activities of 5α-reductase and aromatase inhibitors. J Steroid Biochem 31: 677–683

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Luciano Martini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberto C. Melcangi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fabio Celotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Reproductive Medicine of the University, Steinfurter Str. 107, 4400, Münster, Germany

    Eberhard Nieschlag

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Martini, L., Melcangi, R.C., Celotti, F. (1992). Androgens and the Brain: Role of Testosterone Metabolism. In: Nieschlag, E., Habenicht, UF. (eds) Spermatogenesis — Fertilization — Contraception. Schering Foundation Workshop, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-02815-5_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-02815-5_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-02817-9

  • Online ISBN: 978-3-662-02815-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation