MAPPING OF NEURAL AND SIGNAL-TRANSDUCTION PATHWAYS FOR LORDOSIS IN THE SEARCH FOR ESTROGEN ACTIONS ON THE CENTRAL-NERVOUS-SYSTEM

Estrogen can act on the brain to regulate various biological functions and behavior. In attempts to elucidate the estrogen action, the roden t female reproductive behavior, lordosis, was used as a model. Lordosi s is an estrogen-dependent reflexive behavior and, hence, is mediated by discrete neural pathways that are modulated by estrogen. Therefore, a strategy of mapping the pathways, both neural and biochemical, and examining them for estrogen effect was used to localize and subsequent ly analyze the central action of estrogen. Using various experimental approaches, an 'inverted Y-shaped' neural pathway both sufficient and essential for mediating lordosis was defined. The top portion is a des cending pathway conveying the permissive estrogen influence which orig inated from hypothalamic ventromedial nucleus relayed via midbrain per iaqueductal grey down to medullary reticular formation, the top of the spino-bulbo-spinal reflex are at the bottom. This estrogen influence alters the input-output relationship, shifting the output toward more excitation. With this shift in output, estrogen can enable the otherwi se ineffective lordosis-triggering sensory stimuli to elicit lordosis. In the ventromedial nucleus, the origin of the estrogen influence, a multidisciplinary approach was used to map intracellular signaling pat hways. A phosphoinositide pathway involving a specific G protein and t he activation of protein kinase C was found to be involved in the medi ation of lordosis as well as a probable target of the permissive estro gen action. The action of estrogen on this signal transduction pathway , a potentiation, is consistent with and, hence, may be an underlying mechanism for the estrogen influenced shift toward excitation. Thus, f urther investigation on this specific signal transduction pathway shou ld be helpful in elucidating the action of estrogen on the brain. (C) 1998 Elsevier Science B.V. All rights reserved.