Urinary estrogen and progesterone metabolite concentrations in menstrual cycles of fertile women with non-conception, early pregnancy loss or clinical pregnancy
HUMAN REPRODUCTION
Authors: Venners, Scott A.; Liu, Xue; Perry, Melissa J.; Korrick, Susan A.; Li, Zhiping; Yang, Fan; Yang, Jianhua; Lasley, Bill L.; Xu, Xiping; Wang, Xiaobin
Abstract
BACKGROUND: Knowledge is limited of how estrogen and progesterone variability in fertile women are associated with achieving pregnancy. METHODS: From 1996 to 1998, we enrolled 347 textile workers without hormone treatment in Anhui, China, who provided daily urine and data upon stopping contraception for up to 1 year until clinical pregnancy. Urinary hCG was assayed to detect conception and early pregnancy losses. We compared urinary concentrations of estrone conjugates (E1C) and pregnanediol-3-glucuronide (PdG) in 266 clinical pregnancies, 63 early pregnancy losses and 272 non-conception cycles from 347 women and also in 94 clinical pregnancy and 94 non-conception cycles from the same women. RESULTS: Using generalized estimating equations and relative to 266 clinical pregnancy cycles, log(E1C) was lower in 272 non-conception cycles [beta = -0.3 ng/mg creatinine (Cr); SE = 0.1; P < 0.0001]. On average, daily E1C was 18 ng/mg Cr lower in non-conception cycles than in clinical pregnancy cycles. Relative to 94 clinical pregnancy cycles, log(E1C) was lower in 94 non-conception cycles (beta = -0.4 ng/mg Cr; SE = 0.1; P < 0.0001) from the same women (average difference in daily E1C was 20 ng/mg Cr). The odds of E1C less than the 10th percentile (< 30 ng/mg, Cr) were higher in early pregnancy loss cycles [odds ratio (OR) = 4.8; P = 0.0027] than in. clinical pregnancy cycles in the early luteal phase. Compared with clinical pregnancy cycles, log(PdG) concentrations were lower in non-conception cycles during the follicular phase, but this analysis lacked power for multiple testing. CONCLUSIONS: Estrogen concentrations varied from cycle to cycle, and. higher estrogen was associated with achieving clinical pregnancy.
Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C
PHARMACEUTICAL RESEARCH
Authors: Tamai, I; Nozawa, T; Koshida, M; Nezu, J; Sai, Y; Tsuji, A
Abstract
Purpose. To assess the functional characteristics of human organic anion transporter B (OATP-B) in comparison with those of the known, liver-specific OATP-C. Methods. OATP-B or -C was expressed in HEK293 cells or Xenopus oocytes, and uptakes of estradiol-17 beta -glucuronide and estrone-3-sulfate were measured using radiolabeled compounds. Results. OATP-C transported both estrone-3-sulfate and estradiol-17 beta -glucuronide, whereas OATP-B transported only the former. OATP-C-mediated uptake of estrone-3-sulfate exhibited biphasic saturation kinetics, whereas transports of estradiol-17 beta -glucuronide by OATP-C and estrone-3-sulafte by OATP-B followed single-saturation kinetics. Inhibition kinetics showed that only the high-affinity site for estrone-3-sulfate on OATP-C was shared with glucuronide conjugates. Uptake of [H-3]estrone-3-sulfate by OATP-B was inhibited by sulfate conjugates but not by glucuronide conjugates, whereas its uptake by OATP-C was inhibited by both types of conjugates. Conclusions. OATP-B accepted sulfate conjugates of steroids but not glucuronide conjugates, whereas OATP-C transported both types of steroid conjugates. Transport of estrone-3-sulfate by OATP-B and -C followed single- and biphasic-saturation kinetics, respectively, and the high-affinity site on OATP-C was the same as that for estradiol-17 beta -glucuronide. Other OATPs, OATP-A and OATP-8, reportedly exhibit different preferences for steroid conjugates, and the specific recognition of sulfate conjugates seems to be unique to OATP-B.