Effects Of Synthetic Steroids Research Articles

Effect of synthetic steroids on GABAA receptor binding in rat brain

Neuroactive steroids, like allopregnanolone (A) and pregnanolone (P), bind to specifics sites on the GABAA receptor complex and modulate receptor function. They are capable to inhibit or stimulate the binding of GABAA receptor-specific ligands, like t-butyl-bicyclophosphorothionate, flunitrazepam and muscimol. We have previously characterized a set of oxygen-bridged synthetic steroids (SS) analogs to A or P using synaptosomes. Considering that the subunit composition of the GABAA receptor throughout the central nervous system affects the magnitude of the modulation of the GABAA receptor by NAS, we evaluated the action of two selected SS, in brain sections containing the cerebral cortex (CC) and hippocampus (HC) using quantitative receptor autoradiography. Both SS affected the binding of the three ligands in a similar way to A and P, with some differences on certain CC layers according to the ligand used. One of the SS, the 3α-hydroxy-6,19-epoxypregn-4-ene-20-one (compound 5), behaved similarly to the natural neuroactive steroids. However, significant differences with compound 5 were observed on the HC CA2 region, making it steroid suitable for a specific action. Those differences may be related to structural conformation of the SS and the subunits’ composition present on the receptor complex.

50 years of hormonal contraception-time to find out, what it does to our brain.

Hormonal contraceptives are on the market for more than 50 years and used by 100 million women worldwide. However, while endogenous steroids have been convincingly associated with change in brain structure, function and cognitive performance, the effects of synthetic steroids contained in hormonal contraceptives on brain and cognition have barely been investigated. In this article we summarize the sparse findings, describing brain structural, functional and behavioral findings from the literature and suggest that synthetic steroids may contribute to masculinizing as well as feminizing effects on brain and behavior. We try to identify methodological challenges, explain, how results on endogenous steroids may transfer into research on hormonal contraceptives and point out factors that need to be controlled in the study of hormonal contraceptive dependent effects. We conclude that there is a strong need for more systematic studies, especially on brain structural, functional and cognitive changes due to hormonal contraceptive use. The hormonal contraceptive pill is the major tool for population control. Hence, such behavioral changes could cause a shift in society dynamics and should not stay unattended.

The inhibitory effect of synthetic steroids on proestrous gonadotropin release in the rat.

This study was performed to evaluate the inhibitory effect of synthetic steroids on the hypothalamo-pituitary axis. Six synthetic steroids, used for contraception or other gynecologic indications, were injected to female rats on diestrus 2 (2 mg/kg, sc), and the animals were sacrificed in the afternoon of proestrus. Serum levels of LH, FSH and progesterone, the pituitary contents of LH and FSH, and LH-RH in the median eminence were measured by radioimmunoassays. Among the synthetic steroids tested in this study, norethisterone, d-norgestrel, 3-keto-desogestrel and gestrinone completely blocked the gonadotropin surge on proestrus, showing stronger antigonadotropic activity than progesterone. Desogestrel did not affect proestrous gonadotropin release at this dose. The suppressive effect of danazol could be seen only in a larger dose (20 mg/kg). These findings reconfirmed previously reported results, which demonstrated that the hypothalamo-pituitary complex was a major site of action of these steroids.

Sex hormone binding globulin: effect of synthetic steroids on the assay and effect of oral contraceptives.

The effect that synthetic steroid components of different oral contraceptives have on the assay system for measurement of sex hormones binding globulin (SHBG)-binding capacity, has been examined. Interference with the assay was not demonstrable at therapeutic levels of the drugs. d-Norgestrel was the only steroid studied which bound to SHBG with an affinity comparable to the endogenous sex hormones; it also tended to decrease SHBG-finding capacity, whereas preparations containing low levels of norethisterone increased the binding capacity. We suggest that measurement of changes in SHBG-binding capacity in subjects taking oral contraceptives may prove useful in indicating changes in sex hormone balance, particularly in view of the well-recognised side-effect of these drugs.