title: Biological evaluation of androstene derivatives.
abstract: The effect of several new dihydroepiandrosterone ester derivatives A2-A6 was demonstrated using female cycling mice, which were synchronized for estrus with luteinizing hormone-releasing hormone (LHRH) and injected with the steroids. The binding to the progesterone receptor (PR), was obtained from the cytosol of uteri from adult estrogen-primed rabbits. A1 binds to the PR and inhibited the ovulation in cycling mice stimulated with LHRH. The activity of the endometrium and mammary glands in these mice was markedly reduced as compared to the control. A2, A4, and A5 were not active; nevertheless, A3 binds to the PR with high affinity. However, this steroid did not produce any effect as compared to that observed for the control in the endometrial and mammary glands. A6 binds to the PR with the highest affinity and induces a synergistic activity with progesterone in these tissues. Furthermore, A6 inhibited the ovulation in the same manner as A1. These results suggested that A1 and A6 are blocking the gonadotropin secretion. A1 inhibited the conversion of progesterone to 5α-progesterone. As a result of this, a blockage of the ductal and alveolar epithelial cell proliferation in the mammary and endometrial glands, which depends on 5α-progesterone, was also observed.
authors.affiliation: Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D. F., Mexico.
authors.forename: Mariana
authors.initials: M
authors.lastname: Garrido
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
authors.forename: Mario
authors.initials: M
authors.lastname: García-Lorenzana
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Heuze
authors.forename: Juan
authors.initials: J
authors.lastname: Soriano
authors.forename: Norma
authors.initials: N
authors.lastname: Valencia
authors.forename: Francisco
authors.initials: F
authors.lastname: Cortes
authors.forename: Marisa
authors.initials: M
authors.lastname: Cabeza
mesh_terms: D000736:Androstenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D010060:Ovulation / Q000187:drug effects*; D011374:Progesterone / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D011817:Rabbits; D011980:Receptors, Progesterone / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000736:Androstenes; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone