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Luteal expression of thyroid hormone receptors during gestation and postpartum in the rat.

ABSTRACT: BACKGROUND: Progesterone (P4) is the main steroid secreted by the corpora lutea (CL) and is required for successful implantation and maintenance of pregnancy. Although adequate circulating levels of thyroid hormone (TH) are needed to support formation and maintenance of CL during pregnancy, TH signaling had not been described in this gland. We determined luteal thyroid hormone receptor isoforms (TR) expression and regulation throughout pregnancy and under the influence of thyroid status, and in vitro effects of triiodothyronine (T3) exposure on luteal P4 synthesis. METHODS: Euthyroid female Wistar rats were sacrificed by decapitation on gestational day (G) 5, G10, G15, G19, or G21 of pregnancy or on day 2 postpartum (L2). Hyperthyroidism and hypothyroidism were induced in female Wistar rats by daily administration of thyroxine (T4; 0.25?mg/kg subcutaneously) or 6-propyl-2-thiouracil (PTU; 0.1?g/L in drinking water), respectively. Luteal TR expression of mRNA was determined using real-time reverse-transcription quantitative polymerase chain reaction, and of protein using Western blot and immunohistochemistry. Primary cultures of luteal cells and of luteinized granulosa cells were used to study in vitro effects of T3 on P4 synthesis. In addition, the effect of T3 on P4 synthesis under basal conditions and under stimulation with luteinizing hormone (LH), prolactin (PRL), and prostaglandin E2 (PGE2) was evaluated. RESULTS: TR?1, TR?2, and TR?1 mRNA were present in CL, increasing during the first half and decreasing during the second half of pregnancy. At the protein level, TR?1 was abundantly expressed during gestation reaching a peak at G19 and decreasing afterwards. TR?1 was barely expressed during early gestation, peaked at G19, and diminished thereafter. Expression of TR?1 and TR?1 at the protein and mRNA level were not influenced by thyroid status. T3 neither modified P4 secretion from CL of pregnancy nor its synthesis in luteinized granulosa cells in culture. CONCLUSIONS: This study confirms for the first time the presence of TR isoforms in the CL during pregnancy and postpartum, identifying this gland as a TH target during gestation. TR expression is modulated in this tissue in accordance with the regulation of P4 metabolism, and the abrupt peripartum changes suggest a role of TH during luteolysis. However, TH actions on the CL do not seem to be related to a direct regulation of P4 synthesis.

SUBMITTER: Navas PB

PROVIDER: S-EPMC4046218 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Luteal expression of thyroid hormone receptors during gestation and postpartum in the rat.

Navas Paola B PB Redondo Analía L AL Cuello-Carrión F Darío FD Roig Laura M Vargas LM Valdez Susana R SR Jahn Graciela A GA Hapon María B MB

Thyroid : official journal of the American Thyroid Association 20140601 6

<h4>Background</h4>Progesterone (P4) is the main steroid secreted by the corpora lutea (CL) and is required for successful implantation and maintenance of pregnancy. Although adequate circulating levels of thyroid hormone (TH) are needed to support formation and maintenance of CL during pregnancy, TH signaling had not been described in this gland. We determined luteal thyroid hormone receptor isoforms (TR) expression and regulation throughout pregnancy and under the influence of thyroid status, ...[more]

PMID: 24684177

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Project description:ObjectiveThyroid disorders are commonly concomitant with premature birth; however, indications to start therapy remain unclear due to a lack of gestational age (GA)-specific reference ranges. We aimed to evaluate the age-specific thyroid-stimulating hormone (TSH), free thyroxine (FT4) levels and the correlation between TSH and FT4 serum levels and ultrasound thyroid volume in preterm infants.Materials and methodsThis was an observational, prospective, single-center study of 98 preterm infants born before 33 weeks GA. The infants were divided into the 24-28 weeks and 29-32 weeks GA groups. TSH and FT4 serum levels were measured at two time points: at postnatal age (PNA) 2 weeks and at postmenstrual age (PMA) 32 weeks; the results were compared between groups at two consecutive time points.ResultsThere was a statistically significant between-group difference in FT4 concentration. There was a positive correlation between FT4 and GA at both screening times. FT4 in the 24-28 weeks GA group was significantly lower than in the 29-32 weeks GA group. The mean (standard deviation [SD]) FT4 at PNA 2 weeks was 11.72 ± 2.16 pmol/l for the 24-28 weeks GA group vs. 13.33 ± 1.80 pmol/l for the 29-32 weeks GA group (p<0.001). The mean (SD) FT4 at PMA 32 weeks was 11.96 ± 1.98 pmo/l for the 24-28 weeks GA group vs. 13.33 ± 1.80 pmol/l for the 29-32 weeks GA group (p=0.001). Our results reflect a slow and gradual upward trend of FT4 in the 24-28 weeks GA. It is of interest that the correlation between thyroid volume and FT4 was statistically significant (rho=0.25, p=0.019) for all studied preterm infants. The correlation between thyroid volume and weight was statistically significant for the entire study group (rho=0.37, p<0.001). We did not find statistically significant differences in TSH and FT4 values between consecutive time points at 24-28 weeks GA. The thyroid volume was not significantly different between both groups. The total thyroid volume was 0.26 vs. 0.27 ml for the 24-28 and 29-32 weeks GA groups, respectively.ConclusionThe results of this study indicate that preterm infants require lower FT4 values depending on GA. Moreover, ultrasound thyroid imaging may facilitate the evaluation of questionable thyroid disorders.

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Luteal expression of thyroid hormone receptors during gestation and postpartum in the rat.

Publications

Luteal expression of thyroid hormone receptors during gestation and postpartum in the rat.

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