The Neuroesteroids and Its Association with Carcinogenesis and Drug Use: Impact on the Reproductive Axis

Abstract

Neurosteroids play a crucial role in the regulation of the hypothalamic-pituitary-gonadal axis that modulates the activities of reproductive physiology such as hypothalamic and sex hormone release, ovulation, folliculogenesis, luteogenesis, and male and female sexual response. They also regulate anxiety, memory, stress, and depression. Progesterone-derived neurosteroids are synthesised in the mitochondria of neurons or glial cells from cholesterol or peripheral precursors. The mechanisms of action are varied and include actions on membrane receptors (fast response), ion channel receptors, and cytosolic receptors (slow response), which activate traditional genomic expression. In this chapter, we will focus in particular on progesterone, allopregnanolone, pregnenolone, and dehydroepiandrosterone and their effects on the hypothalamic-pituitary-gonadal axis, drug use, and on reproductive tissues carcinogenesis. There is evidence that these neurosteroids may influence the physiological and behavioural effects induced by drugs such as cocaine and cannabis. In turn, these drugs can affect serum levels of some neurosteroids at different stages of life. This section will discuss human and animal findings examining the interaction between neurosteroids and the most common drugs of abuse. In particular, the neurosteroid allopregnanolone, a progesterone metabolite, will be highlighted as a molecule of interest in several psychiatric and neurological pathologies, as well as for affecting several important ovarian parameters that could impair reproduction.