Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

Front Neuroendocrinol. 2020 Jan:56:100804. doi: 10.1016/j.yfrne.2019.100804. Epub 2019 Nov 2.

Abstract

The nervous system, in addition to be a target for steroid hormones, is the source of a variety of neuroactive steroids, which are synthesized and metabolized by neurons and glial cells. Recent evidence indicates that the expression of neurosteroidogenic proteins and enzymes and the levels of neuroactive steroids are different in the nervous system of males and females. We here summarized the state of the art of neuroactive steroids, particularly taking in consideration sex differences occurring in the synthesis and levels of these molecules. In addition, we discuss the consequences of sex differences in neurosteroidogenesis for the function of the nervous system under healthy and pathological conditions and the implications of neuroactive steroids and neurosteroidogenesis for the development of sex-specific therapeutic interventions.

Keywords: 5α-Reductase; Affective disorders; Alzheimer's disease; Diabetic neuropathy; LXR ligands; Multiple sclerosis; Parkinson's disease; Stroke; TSPO ligands; Traumatic brain injury.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / metabolism
  • Animals
  • Brain / metabolism
  • Female
  • Gonadal Steroid Hormones / biosynthesis
  • Gonadal Steroid Hormones / physiology
  • Humans
  • Male
  • Mental Disorders / epidemiology
  • Multiple Sclerosis / epidemiology
  • Multiple Sclerosis / metabolism
  • Nervous System / metabolism*
  • Nervous System Diseases / epidemiology
  • Nervous System Diseases / metabolism*
  • Neurodegenerative Diseases / epidemiology
  • Parkinson Disease / epidemiology
  • Parkinson Disease / metabolism
  • Sex Characteristics*
  • Steroids / analysis*
  • Steroids / biosynthesis*

Substances

  • Gonadal Steroid Hormones
  • Steroids