The effect of progesterone replacement on gene expression in the corpus luteum during induced regression and late luteal
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RESEARCH
Open Access
The effect of progesterone replacement on gene expression in the corpus luteum during induced regression and late luteal phase in the bonnet monkey (Macaca radiata) Padmanaban S Suresh, Kadthur C Jayachandra, Rudraiah Medhamurthy*
Abstract Background: In higher primates, although LH/CG play a critical role in the control of corpus luteum (CL) function, the direct effects of progesterone (P4) in the maintenance of CL structure and function are unclear. Several experiments were conducted in the bonnet monkey to examine direct effects of P4 on gene expression changes in the CL, during induced luteolysis and the late luteal phase of natural cycles. Methods: To identify differentially expressed genes encoding PR, PR binding factors, cofactors and PR downstream signaling target genes, the genome-wide analysis data generated in CL of monkeys after LH/P4 depletion and LH replacement were mined and validated by real-time RT-PCR analysis. Initially, expression of these P4 related genes were determined in CL during different stages of luteal phase. The recently reported model system of induced luteolysis, yet capable of responsive to tropic support, afforded an ideal situation to examine direct effects of P4 on structure and function of CL. For this purpose, P4 was infused via ALZET pumps into monkeys 24 h after LH/P4 depletion to maintain mid luteal phase circulating P4 concentration (P4 replacement). In another experiment, exogenous P4 was supplemented during late luteal phase to mimic early pregnancy. Results: Based on the published microarray data, 45 genes were identified to be commonly regulated by LH and P4. From these 19 genes belonging to PR signaling were selected to determine their expression in LH/P4 depletion and P4 replacement experiments. These 19 genes when analyzed revealed 8 genes to be directly responsive to P4, whereas the other genes to be regulated by both LH and P4. Progesterone supplementation for 24 h during the late luteal phase also showed changes in expression of 17 out of 19 genes examined. Conclusion: These results taken together suggest that P4 regulates, directly or indirectly, expression of a number of genes involved in the CL structure and function.
Background In mammals, the secretion of progesterone (P4) by corpus luteum (CL) is absolutely essential for establishment and, in some species, maintenance of pregnancy. In higher primates, LH and chorionic gonadotropin (CG) have been suggested to be the principal trophic factors responsible for P4 secretion in the CL [1]. Whether P4 plays a role in the maintenance of structure and function of CL has not been fully elucidated in higher * Correspondence: [email protected] Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore-560012, India
primates. Rothchild postulated that P4 is the primary stimulus of its own secretion and that intraluteal P 4 , among other effects such as control of structural integrity and steroidogenic capacity, is responsible for regulation of pro
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