Hypothyroidism prolongs corpus luteum function in the pregnant rat

Abstract

It has been shown that hypothyroidism in the rat produces a prolongation of pregnancy associated with a delay in the fall of circulating progesterone (P 4 ) at term. The aim of the present work is to determine whether the delayed P 4 decline in hypothyroid mother rats is due to a retarded induction of P 4 degradation to 20aOH P 4 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, P 4 , PGF2a, and PGE2) involved in luteal regulation at the end of pregnancy and, by semiquantitative RT-PCR, the expression of factors involved in P 4 synthesis (CytP450scc, StAR, 3bHSD, PRLR) and metabolism (20aHSD, PGF2aR, iNOS and COX2). Our results show that the delay in P 4 decline and parturition is the resultant of retarded luteal regression, caused by a combination of decreases in luteolytic factors, mainly luteal PGF2a, 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 20aHSD mRNA and protein (measured by western blot analysis) expression, which in the presence of unchanged expression of the factors involved in P 4 synthesis results in elevated luteal and circulating P 4 that prolonged pregnancy and also may favor longer survival of the corpus luteum.

Structural, functional, and lectin histochemical characteristics of rat ovaries and endometrium in experimental hyper- and hypothyroidism

“…The present data on increased folliculogenesis and inhibited corpora lutea formation under hypothyroid influence are to a certain extent at variance with the results reported by Hapon et al [18], who described prolonged activity of corpus luteum gravidarum in hypothyroid rats. At the same time, the present results are in good agreement with the clinical observations of polycystic ovary syndrome associated with hypothyroidism [19].…”

Relationships between thyroid hormones and serum energy metabolites with different patterns of postpartum luteal activity in high-producing dairy cows

“…No information is available regarding changes in the blood thyroid hormones concentrations associated with the occurrence of PLP in postpartum dairy cows. However, the corpus luteum function was prolonged when adult rats underwent an induced hypothyroxinemia (Hapon et al, 2007). The prolongation of the corpus luteal function in rats was attributed to a combination of factors including the decrease in luteal prostaglandin F 2a and increased synthesis of circulating prostaglandin E 2 .…”

Hyperthyroidism advances luteolysis in the pregnant rat through changes in prostaglandin balance

“…For luteal P, PGE 2 , and PGF 2a quantifications, CL and sera were extracted and the hormones measured by RIA using commercial kits as previously described (17).…”

“…Proteins isolated from the phenol-ethanol supernatant obtained from RNA isolation using TRIZOL reagent (Invitrogen Life Technologies) were analyzed for 20aHSD abundance by Western blot as described previously (17). Relative levels of 20aHSD protein were expressed as the ratio of signal intensity for the protein relative to that of a-tubulin.…”

“…Hypothyroid pregnant rats have delayed luteolysis and delivery (16) caused by a combination of decreased luteal PGF 2a and increased PGE 2 and PRL (17). Conversely, experimental hyperthyroidism advances the decrease in circulating P and parturition by approximately 12 hours (10,18), suggestive of premature luteolysis.…”