 |
|
| MULTIPLE OVARIAN HORMONE EFFECTS ON BRAIN STRUCTURE AND FUNCTION Bruce S. McEwen, Ph.D., Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York Ovarian steroids have numerous effects on the brain throughout the lifespan, beginning during gestation and continuing into senescence. Besides regulating reproductive functions, ovarian steroids also have widespread effects throughout the brain, on catecholaminergic neurons and serotonergic pathways and on the basal forebrain cholinergic system. Regulation of the serotonergic system appears to be linked to the presence of estrogen and progestin sensitive neurons in the midbrain raphe, whereas the ovarian steroid influences upon cholinergic function involves induction of choline acetyltransferase and acetylcholinesterase according to a sexually dimorphic pattern. Sensitivity to pain in women may be dependent on some or all of these actions, or on other neural systems that are not yet well described in terms of hormonal sensitivity. Another important action of ovarian hormones is regulation of synapse turnover in the hippocampus during the 4-5d estrus cycle of the female rat. Formation of new excitatory synapses is induced by estradiol and involves NMDA receptors, whereas down-regulation of these synapses involves intracellular progestin receptors. In the human brain, estrogen replacement therapy is associated with improvements in episodic and declarative memory, known to depend on the hippocampus. There are developmentally-programmed sex differences in many of these neural systems that influence affect and cognition, and there is some limited evidence regarding pain. During the period of development when testosterone is elevated in the male, aromatase and estrogen receptors are transiently expressed in cortical regions, and recent data on behavior and synapse induction strongly suggest that this pathway is involved in the masculinization or defeminization of hippocampal structure and function. Androgens and androgen receptors also play a role in the actions of testosterone to produce sex differences in other neural systems in which sex hormones have regulatory effects in adult life.
|