Roles Of Thyroid Hormones During Ovarian Follicular Development In Rats

Thyroid hormones (THs) play a critical role in ovarian follicular development, maturation and the maintenance of various endocrine functions. Thyroid dysfunction can affect puberty onset, estrous cyclicity, ovulatory disturbances and alteration follicular development, as well as change the NOS activity. Therefore, this study was designed to elucidate the effect of thyroid hormones on ovarian follicular development, the TRal and NOS isoforms expression, puberty onset and estrous cyclicity. The aim of the present study was:1. Effect of thyroid hormones on ovarian follicular development in neonatal and immature ratsThirty female post-lactation mother of Sprague-Dawley rat pups were randomly divided into three groups:control, hyperthyroid (hyper) and hypothyroid (hypo). On postnatal days (PND) 10 and 21, body weights, serum hormones, ovarian histologic changes, and immunohistochemistry of thyroid hormone receptor alpha 1 (TRal) and nitric oxide synthase types (NOS), and NOS activities were determined. The data showed that body weights significantly decreased in both hyper and hypo groups compared with the control group (P<0.05). In addition, the hyper group had increased serum concentrations of T3, T4 and E2; whereas the hypo group manifested reduced serum concentrations of T3, T4 and E2 on PND 10 and 21. The hyper and hypo groups showed significantly reduced total number of primordial, primary and secondary follicles on PND 10 and 21 compared with the control group (P<0.05). Similarly, antral follicle numbers in the hyper and hypo groups were significantly decreased on PND21 compared with the control group (P<0.05). Immunostaining results indicated that TRal and NOS were expressed in ovarian surface epithelium and oocytes of growing and antral follicles, and with strong staining in the granulosa and theca cells of follicles. NOS activities were significantly augmented in the hyper, but diminished in the hypo groups on PND10 and 21. In summary, our findings suggested that THs played important roles in ovarian functions and in the regulation of NOS activity. Our results also indicated that a relationship existed between the THs and NO signaling pathways during the process of ovarian follicular development in neonatal and immature rats.2. Nitric oxide (NO) and thyroid hormone receptor alpha 1 (TRal) in these disorders using immature hyper-thyroid (hyper-T) and hypo-thyroid (hypo-T) ratsThirty immature female Sprague-Dawley rats at 21 days of age were randomly divided into three groups:control, hyperthyroid (hyper) and hypothyroid (hypo). We found that neuronal NOS (nNOS) and TRal were presented in oocytes, granulosa cells and theca cells. Ovarian nitric oxide (NO) contents and constitutive NOS (cNOS) activities from hyper-T rats were significantly decreased compared with those from controls and hypo-T rats. Moreover, numbers of antral follicles were reduced significantly in hyper-T rats, and numbers of preantral follicles were decreased in the hypo-T rats. The data showed that the hyper-T group had increased serum concentrations of total T3 and T4; whereas the hypo-T group manifested reduced serum concentrations of total T3 and T4 on day 33. In addition, the serum levels of estradiol (E2) were decreased both in hyper-T and in hypo-T compared with control group. While, serum levels of E2 in hyperthyroidism were lower than that in hypothyroidism. In conclusions, thyroid hormone is necessary for folliculogenesis, an association exists between the thyroid hormone and NO signaling pathways during the process of ovarian follicular development in immature rats. In hyperthyroidism, thyroid hormone and TRal induced estrogen deficiency negatively modified the function of nNOS to inhibit NO synthesis and folliculogenesis. While in hypothyroidism, the development of primary follicles was inhibited, but the antral follicular development was improved.3. Effects of thyroid hormones in puberty onset and estrous cyclicity of young adult ratOur study was conducted to elucidate the effect of thyroid hormones on puberty onset and estrous cyclicity, and ovarian expression patterns and immunolocalization of TRal in hyperthyroid thyroxine (T4) and hypothyroid propyilthiyouracil (PTU)-treated young adult rats. Our results showed that body and ovarian weights were significantly decreased in hyper- and hypo-thyroid animals compared to controls. Furthermore, days of vaginal opening were delayed and the estrous cycle became irregular in the treated groups compared to controls. Serum concentrations of total T3 and T4, P4 and FSH were increased, while concentrations of E2 and LH were decreased after injection of T4. Serum levels of total T3 and T4, E2, P4, FSH and LH were diminished after treating with PTU. Numbers of ovarian secondary and antral follicles were decreased in the T4 and PTU groups. Ovaries of treated rats contained considerably more atretic antral follicles and a reduced number of corpora lutea compared to controls. The result of immunoblotting and immunohistochemical staining showed that TRal was involved in the process of ovarian follicular development.In conclusions, our findings suggested that thyroid hormone play important roles in hormones alteration, ovarian follicular development, functions and in the regulation of NOS activity in neonatal and immature rats. Furthermore, our findings provide the first evidence of expression of TRal in ovarian tissues, and those thyroid hormones play regulatory roles in the induction of puberty onset and maintenance of estrous cycles in young adult rats.