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Molecular Human Reproduction, Vol. 7, No. 6, 567-572, June 2001
© 2001 European Society of Human Reproduction and Embryology


Uterine physiology

Progesterone inhibition of functional leptin receptor mRNA expression in human endometrium

Hisato Koshiba, Jo Kitawaki1,, Hiroaki Ishihara, Noriko Kado, Izumi Kusuki, Katsumi Tsukamoto and Hideo Honjo

Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

Abstract

Leptin is secreted by adipocytes and regulates appetite through interaction with hypothalamic leptin receptors (OB-R). Leptin is involved in the stimulation of reproductive functions, and local expression of leptin and OB-R in the ovary, oocyte, embryo, and placenta might play a role in early development. The mRNA and protein of the long form leptin receptor (OB-RL) but not of leptin are expressed in the human endometrium and the abundance of OB-R mRNA expression varies during the menstrual cycle with a peak in the early secretory phase. We examined the steroidal regulation of OB-RL mRNA expression. Northern blot analyses showed that in organ-cultured proliferative endometrial specimens, oestradiol (10–9 and 10–8 mol/l) had no acute effect on the OB-RL mRNA expression, whereas oestradiol plus progesterone (10–8, 10–7 and 10–6 mol/l) or medroxyprogesterone acetate (10–8 and 10–7 mol/l) suppressed the expression by ~50%. This progestin-induced suppression was blocked by a concomitant addition of mifepristone. Additionally, incubation of endometrial specimens in the presence of leptin resulted in the phosphorylation of its intracellular target, STAT3 (signal transducer and activator of transcription 3). These results indicate that, in the human endometrium, progestins act via the progesterone receptors to suppress functional OB-RL mRNA expression, and may thereby alter the sensitivity of the endometrium to leptin.

endometrium/intracellular signalling/leptin receptor/oestrogen/progestin

Notes

1 To whom correspondence should be addressed. E-mail: kitawaki{at}koto.kpu-m.ac.jp


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