DAHFMO, Unit of Histology and Medical Embryology, Sapienza, University of Rome, Rome, Italy.
IVIRMA Global Research Alliance, GENERA, Clinica Valle Giulia, Rome, Italy.
J Endocrinol Invest. 2024 Jul;47(7):1719-1732. doi: 10.1007/s40618-023-02269-z. Epub 2024 Jan 8.
To evaluate the impact of high thyroid stimulating hormone (TSH) levels on human granulosa-luteal (hGL) cells.
hGL cells were isolated from follicular aspirates derived from patients undergoing IVF treatment without any thyroid disorder (serum TSH 0.5-2 mU/L). Cells were cultured at 37 °C in DMEM, supplemented with 5% FBS. The cells were treated with 1 nM LH and increasing concentrations of TSH. At the end of culture, conditioned medium and cells were collected to analyze progesterone production, cell viability, and mRNA levels of genes involved in the steroidogenesis process. Human ovarian tissues were analyzed for TSH receptor (TSHR) expression by IHC.
The expression of TSHR was detected in human corpus luteum by IHC and in hGL by RT-PCR. In hGL cells, TSH treatment did not modulate progesterone production nor the expression of steroidogenic genes, such as p450scc and HSD3b 1/2. However, TSH induced a dose-dependent increase in cell death. Finally, TSH did not affect LH-induced p450scc and HSD3b1/2 expression while LH partially reverted TSH negative effect on cell death in hGL.
Elevated TSH levels in hypothyroid women may be associated with impaired CL functioning and maintenance. These findings open a new line of research for the importance of the treatment of women with thyroid dysfunction that could contribute to the onset of infertility.
评估高甲状腺刺激素（TSH）水平对人颗粒黄体（hGL）细胞的影响。
从接受 IVF 治疗且无甲状腺疾病的患者的卵泡抽吸物中分离出 hGL 细胞（血清 TSH 0.5-2 mU/L）。将细胞在 37°C 的 DMEM 中培养，补充 5% FBS。用 1 nM LH 和递增浓度的 TSH 处理细胞。培养结束后，收集条件培养基和细胞，分析孕激素产生、细胞活力以及参与类固醇生成过程的基因的 mRNA 水平。通过免疫组化分析人卵巢组织中 TSH 受体（TSHR）的表达。
免疫组化检测到 hCG 中的 TSHR 表达和 hGL 中的 TSHR 表达。在 hGL 细胞中，TSH 处理不会调节孕激素产生或类固醇生成基因（如 p450scc 和 HSD3b1/2）的表达。然而，TSH 诱导细胞死亡呈剂量依赖性增加。最后，TSH 不影响 LH 诱导的 p450scc 和 HSD3b1/2 表达，而 LH 部分逆转了 TSH 对 hGL 细胞死亡的负效应。
甲状腺功能减退妇女中 TSH 水平升高可能与黄体功能障碍和维持有关。这些发现为甲状腺功能障碍妇女的治疗重要性开辟了新的研究途径，这可能有助于不孕的发生。
