Adrenomedullin in rat follicles and corpora lutea: expression, functions and interaction with endothelin-1
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RESEARCH
Open Access
Adrenomedullin in rat follicles and corpora lutea: expression, functions and interaction with endothelin-1 Lei Li1, Wai-Sum O2,3* and Fai Tang1,4
Abstract Background: Adrenomedullin (ADM), a novel vasorelaxant peptide, was found in human/rat ovaries. The present study investigated the interaction of ADM and endothelin-1 (ET-1) in follicles and newly formed corpora lutea (CL) and the actions of ADM on progesterone production in CL during pregnancy. Methods: The peptide and gene expression level of adrenomedullin in small antral follicles, large antral follicles and CL was studied by real-time RT-PCR and EIA. The effect of ADM treatment on oestradiol production in 5-day follicular culture and on progesterone production from CL of different pregnant stages was measured by EIA. The interaction of ADM and ET-1 in follicles and CL at their gene expression level was studied by real-time RT-PCR. Results: In the rat ovary, the gene expression of Adm increased during development from small antral follicles to large antral follicles and CL. In vitro treatment of preantral follicular culture for 5 days with ADM increased oestradiol production but did not affect follicular growth or ovulation rate. The regulation of progesterone production by ADM in CL in culture was pregnancy-stage dependent, inhibitory at early and late pregnancy but stimulatory at mid-pregnancy, which might contribute to the high progesterone production rate of the CL at midpregnancy. Moreover, the interaction between ADM and ET-1 at both the production and functional levels indicates that these two vasoactive peptides may form an important local, fine-tuning regulatory system together with LH and prolactin for progesterone production in rat CL. Conclusions: As the CL is the major source of progesterone production even after the formation of placenta in rats, ADM may be an important regulator in progesterone production to meet the requirement of pregnancy.
Background First discovered in human pheochromatocytoma tissue in 1993 [1], adrenomedullin (ADM) is highly conserved across species [2-5] and is widely expressed in various organs and tissues, including heart, kidney, lung, adrenal gland [6] and reproductive organs, such as the ovary [7-10], the uterus [7,11], the oviduct [12], the testis [13-16], the prostate [17,18], and the epididymis [19]. ADM belongs to the calcitonin family with a high sequence homology to calcitonin gene-related peptide (CGRP). ADM can bind to the CGRP receptor in several types of tissues [20,21], but specific ADM receptors that are insensitive to CGRP receptor antagonist have been * Correspondence: [email protected] 2 Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China Full list of author information is available at the end of the article
identified [22]. McLatchie et al. [23] demonstrated that the combination of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP) isoforms determines the ligand selectivit
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