Endocrine Abstracts

Although neuroactive steroids are well characterized, their physiological relevance in human pregnancy remains indecisive. Hence, we attempted to derive this information from the combination of our metabolomic data, pharmacological data found in the literature and knowledge contained in gene expression databases. These results indicate that GABAergic steroids influence maternal CNS but have limited effect in the fetal brain and maternal and fetal periphery, partly because of the low expression of steroid-sensitive GABAA-R subunits and partly due to lower GABAergic steroid levels in the circulation compared to the brain. Placental overexpression of steroid low-sensitive GABAA-R ε subunits may be ascribed to compensation effect providing a space for modulatory effects of non-steroidal GABAergic modulators in the tissue with excessive amounts of GABAergic steroids. A specific role of GABAergic steroids may be expected for the GABAA-R π subunit, which is preferentially expressed in the uterus and which decreases at the onset of labor. Metabolomic, tissue expression and pharmacological data also indicate that the mechanism suggested by some authors(who demonstrated inhibition of HPA axis by GABAergic steroids in the rat pregnancy), may be also effective in human. Rapid withdrawal from the excessive concentrations of GABAergic steroids postpartum indicate that the increased expression of steroid-less sensitive GABAA-R subunits is linked to the mechanism participating in the pathophysiology of postpartal depressions. In contrast to specific expression of steroid-sensitive GABAA-R subunits, the uniform expression of steroid-sensitive glycinergic subunits points to the neuro-inhibitory effect of pregnenolone in the CNS but neuro-excitatory effect of its sulfate in the pregnancy-related peripheral tissues like uterus, cervix and placenta.

The trial was approved by the Ethic Committee. Grants IGA NT/11513 and NT/12211 and advanced education of own staff in clinical and molecular endocrinology (CZ.2.17/1.1.00/32386) supported the study.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.