IN VITRO METABOLISM OF [6,7-3H]NORETHYNODREL IN THE HUMAN ENDOMETRIUM AND THE MYOMETRIUM

Abstract

ABSTRACT The human endometrium and the myometrium have the capacity to convert [6,7-3H]norethynodrel to norethindrone, 17α-ethynyl-3α,17β-dihydroxy-5-(10)-oestrene and two other unidentified metabolites. Under in vitro conditions, 80–90 % of 3H-norethynodrel was converted to its metabolites within 90 min. The metabolites formed were the same for both the endometrium and the myometrium. The amount of norethynodrel converted to its metabolites was more in the proliferative phase than in the secretory phase. Among the subcellular fractions of the myometrium, mitochondrial and microsomal fractions metabolised norethynodrel to norethindrone and two polar metabolites with low chromatographic mobility. In the myometrial 105 000 × g supernatant fraction, 17α-ethynyl-3α,17β-dihydroxy-5(10)-oestrene was formed in addition to norethindrone and the polar metabolites. The significance of the formation of norethindrone – a potent oral progestin as a product of the metabolism of norethynodrel and its possible action at the uterine level in the control of fertility is discussed.