Hypothyroidism prolongs corpus luteum function in the pregnant rat.
It has been shown that hypothyroidism in the rat produces a prolongation of pregnancy associated with a delay in the fall of circulating progesterone (P4) at term. The aim of the present work is to determine whether the delayed P4 decline in hypothyroid mother rats is due to a retarded induction of P4 degradation to 20alphaOH P4 or to a stimulation of its synthesis, and to investigate the possible mechanisms that may underlie the altered luteal function. We determined by RIA the circulating profile of the hormones (TSH, PRL, LH, P4, PGF2alpha, and PGE2) involved in luteal regulation at the end of pregnancy and, by semiquantitative RT-PCR, the expression of factors involved in P4 synthesis (CytP450scc, StAR, 3betaHSD, PRLR) and metabolism (20alphaHSD, PGF2alphaR, iNOS and COX2). Our results show that the delay in P4 decline and parturition is the resultant of retarded luteal regression, caused by a combination of decreases in luteolytic factors, mainly luteal PGF2alpha, iNOS mRNA expression and also circulating LH, and increased synthesis or action of luteotrophic factors, such as luteal and circulating PGE2 and circulating PRL. All these changes may be direct causes of the decreased 20alphaHSD mRNA and protein (measured by western blot analysis) expression, which in the presence of unchanged expression of the factors involved in P4 synthesis results in elevated luteal and circulating P4 that prolonged pregnancy and also may favor longer survival of the corpus luteum.
Hapon
María Belén
MB
Laboratorio de Reproducción y Lactancia, IMBECU-CONICET, Mendoza, Argentina. bhapon@lab.cricyt.edu.ar
Motta
Alicia B
AB
Ezquer
Marcelo
M
Bonafede
Melisa
M
Jahn
Graciela A
GA
D015089:20-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003338:Corpus Luteum / Q000378:metabolism; D003340:Corpus Luteum Maintenance / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007037:Hypothyroidism / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000097:blood*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D007986:Luteinizing Hormone; D015089:20-Hydroxysteroid Dehydrogenases; D052247:Nitric Oxide Synthase Type II; D002786:Cholesterol Side-Chain Cleavage Enzyme; D051546:Cyclooxygenase 2