title: Importance of A-ring substitution of estrogens for the physiology and pharmacology of reproduction.
abstract: Estrogens substituted in the ortho-position of the phenolic hydroxy-group with an additional hydroxy- or methoxy-group are quantitatively important estrogen metabolites; first isolated and identified from the urine of man and rodents have been demonstrated in blood and different organs, e.g. the pituitary and hypothalamus. The physiological importance of the preeminent representatives of this group, the 2- and 4-hydroxyestrogens, the so-called catecholestrogens, is still equivocal. For example, numerous in vivo investigations in rodents have demonstrated that gonadotrophin secretion is influenced by these catecholestrogens. However, depending on the position of the A-ring substituent, major potency differences have been observed. The significant discrepancies between the quantitative and qualitative effects of catecholestrogens in in vitro and in vivo experiments have been presented and explained on the basis of different receptor affinities and the pharmacokinetics of catecholestrogens. An array of A-ring-substituted steroid model substances has been tested with respect to the effects of 2- and/or 4-substitution on stimulation or blockade of the estrogenic potency.
mesh_terms: D000818:Animals; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D002393:Estrogens, Catechol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004967:Estrogens; D002393:Estrogens, Catechol; D007986:Luteinizing Hormone