Differential distribution of the 5-α-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?

https://doi.org/10.1016/0022-4731(87)90040-9Get rights and content

Abstract

In the brain of several animal species testosterone is converted into a series of 5-α-reduced metabolites, and especially into 17-β-hydroxy-5-α-androstan-3-one (DHT), by the action of the enzyme 5-α-reductase. The formation of DHT has never been evaluated in the white matter structures of the brain, which are composed mainly of myelinated axons. The experiements here described were performed in order to study, in the rat and the mouse, the DHT forming activity of several white matter structures, in comparison with that of the cerebral cortex and of the hypothalamus. Two sampling techniques were used in the rat: (1) microdissection under a stereo-microscope from frozen brain sections of fragments of corpus callosum, optic chiasm and cerebral cortex; (2) fresh tissue macrodissection of subcortical white matter, cerebral cortex and hypothalamus. Only macrodissection was used in the mice.

The data show that, independently from the sampling technique used, there are considerable quantitative differences in the distribution pattern of the 5-α-reductase activity within different brain structures. Both in the rat and in the mouse, the enzyme appears to be present in higher concentrations in the white matter structures, than in the cerebral cortex and in the hypothalamus. The present results clearly show that the subcortical white matter and the corpus callosum are at least three times as potent as the cerebral cortex in converting testosterone into DHT. An even higher 5-α-reductase activity has been found in the optic chiasm. Further work is needed in order to understand the possible physiological role of DHT formation in the white matter structures.

References (31)

  • M.E. Jurman et al.

    Testosterone 5-alpha-reductase in spinal cord of Xenopus laevis

    J. Neurochem.

    (1982)
  • G.V Callard

    Aromatization in brain and pituitary; an evolutionary perspective

  • R. Massa et al.

    The metabolism of sex steroids in the bird CNS and pituitary

  • R.B. Jaffe

    Testosterone metabolism in target tissues: hypothalamic and pituitary tissues of the adult rat and human fetus, and immature rat epiphysis

    Steroids

    (1969)
  • Z. Kniewald et al.

    Conversion of testosterone into 5-alpha-androstan-17-beta-ol-3-one at the anterior pituitary and hypothalamic level

  • Cited by (54)

    • Reproductive performance is associated with seasonal plasma reproductive hormone levels, steroidogenic enzymes and sex hormone receptor expression levels in cultured Asian yellow pond turtles (Mauremys mutica)

      2021, Comparative Biochemistry and Physiology Part - B: Biochemistry and Molecular Biology
      Citation Excerpt :

      Initiation of the sex hormone synthesis pathway is marked by gonadal production of steroidogenic acute regulatory protein (StAR) in mouse, Mus musculus (Clark et al., 1994). StAR is considered to be an important rate-limiting step in sex hormone synthesis (Fig. 1A), and functions to transport the raw material cholesterol that is synthesized by steroid hormones to mitochondrial inner membrane (Arakane et al., 1998), where cholesterol is converted to different intermediate products under the catalysis of steroidogenic enzymes (Negricesi, 1987; Lephart, 1996; Mindnich et al., 2004; Guzmán et al., 2018). Many studies have shown that steroidogenic enzyme plays an important role in gonadal development and reproductive activity across seasonally breeding vertebrates such as Acanthopagrus schlegeli, mare, Anolis carolinensis and lizards (Albrecht et al., 2001; Tomy et al., 2010; Rosati et al., 2016, 2017, 2019, 2020; Christine and Rachel, 2018; Santillo et al., 2019), however, little research about relationship between steroidogenic enzyme expression levels and reproductive capability has not been reported in turtles.

    • Neurosteroid biosynthesis: Enzymatic pathways and neuroendocrine regulation by neurotransmitters and neuropeptides

      2009, Frontiers in Neuroendocrinology
      Citation Excerpt :

      Beside 3α-HSD types 2 and 3, 20α(3α)-HSD is also actively expressed in the human brain [581] whereas 3α-HSD type 1 is not [722,731,732,733]. In vitro and in vivo studies have demonstrated the presence of 3α-HSD bioactivity in the CNS of rodents [115,116,126,189,340,367,368,443,578] and primates [85,86,133,637]. In rat, the highest activity is found in the olfactory bulb and olfactory tubercle [340,578] indicating that the 3α-HSD protein detected in this region [141,340] corresponds to a biologically active form of the enzyme.

    • Born gay? The psychobiology of human sexual orientation

      2003, Personality and Individual Differences
    • Biosynthesis and action of neurosteroids

      2001, Brain Research Reviews
    • Progesterone-transforming enzyme activity in the hypothalamus of the male rat

      1999, Journal of Steroid Biochemistry and Molecular Biology
    View all citing articles on Scopus
    View full text