Estrogen and colinergic muscarinic neurotransmission: expression of receptors, intracellular signaling and its interactions in the central nervous system and in the male reproductive tract

Abstract

Objectives of the project: 1) to identify and characterize the subtypes of muscarinic receptors (mAChR) and investigate the role of estrogen in the expression and in the intracellular signaling induced by these receptors in efferent and epididymal ductules in mice. The expression of the subtypes of estrogen receptors (ER), the length of the epididymis, will also be characterized. These studies will permit a better understanding of the action of the estrogen itself in these tissues and of its interaction with cholinergic transmission, important in the control of male (in)fertility; 2) investigate the role of estrogen in the expression of catalytically active acetylcholinesterase (AChE), in the expression and signaling induced by the subtypes of mAChR, using tissue or culture of primary cells (cells of the glia and neurons) of hippocampus of mice. The effect of the estrogen on the mAChR could have relevant significance in the deficit of memory of women after menopause and in the neurodegenerative processes, where the real role of estrogen is not known. Relevance of the work: To relate the effects of estrogen and of the stimulation of mAChR to mechanisms of acquisition/maintenance of male fertility and neuroprotection induced by estrogen. Experimental Strategies: 1) Studies of the male reproductive tract: there is data in the literature on expression of ER only in the efferent ductule of mice. We will broaden the study of the expression and location of ER (REα and REβ); along the epididymis. We will also evaluate the expression and location of mAChR in efferent ductules and along the epididymis of mice in different phases of development. After this characterization, we will evaluate the effect of pure anti-estrogenetic ICI 182,780 in the expression of mAChR (rnRNA and protein). We will then go on to identify the intracellular signaling induced by mAChR and its modulation by the estrogens in the tissues mentioned above. (AU)