Steroid hormone-induced effects on membrane dynamics and function as potential mechanism for brain sexual dimorphism

• Main Author: Whiting, K. P.
• Published: Swansea University 1995
• Subjects: 612.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636590

This thesis examines the possibility that steroid hormones exert many of their rapid, non-genomic effects by changing the dynamics and functions of membranes. The lipophilic molecules intercalate into bilayers, altering the movement of phospholipids and subsequently integral protein mobility. The side chain or group at position 17 of steroid hormones appears to have the greatest influence on fluidity, with the group at position 3 and its spatial orientation within the bilayer, exerting a lesser effect on lipid movement. Steroid-induced changes in the oligomeric state of a membrane-bound protein, the Ca<SUP>2+</SUP> ATPase of sarcoplasmic reticulum membranes, directly influences the enzyme activity. Steroidal action on membrane fluidity is reduced by increasing the cholesterol content within the bilayer, since this molecule orders the lipid environment. The cholesterol content and fluidity varies between membranes, and over development. This makes membranes most susceptible to non-genomic steroid action during a critical period of sexual differentiation in mammals when bilayers are most fluid. Steroid hormones may, therefore, act non-genomically on maturating membranes to control sexual dimorphism and development. Such actions may also be implicated in the effects of xenobiotic oestrogenic compounds.