Context-dependent effects of triiodothyronine on progesterone secretion and cAMP responses in rat ovarian tissues

Abstract Thyroid hormones are essential regulators of metabolism and reproduction; however, their direct influence on ovarian steroidogenesis remains incompletely understood. This study examined the context-dependent effects of triiodothyronine (T3) on progesterone secretion and cyclic adenosine monophosphate (cAMP) signaling in rat ovarian tissues. Using in vitro static culture and in vivo thyroid status models, we assessed the impact of T3, thyroxine (T4), porcine follicle-stimulating hormone (pFSH), and human chorionic gonadotropin (hCG) across estrous phases. Progesterone and cAMP levels were quantified by radioimmunoassay (RIA). T3 significantly enhanced basal cAMP synthesis and progesterone secretion in non-luteal ovarian cells, particularly when administered prior to hCG stimulation. This priming effect was consistent across proestrus, estrus, and diestrus phases. Conversely, both T3 and T4 dose-dependently suppressed basal and hCG-induced progesterone secretion in luteal tissues and isolated luteal cells. In vivo experiments confirmed that hyperthyroid conditions elevated ovarian cAMP content, whereas hypothyroidism induced by propylthiouracil (PTU) sensitized gonadotropin responsiveness. Collectively, these findings demonstrate that T3 exerts dual and context-dependent effects on ovarian progesterone production, which are closely associated with modulation of cAMP signaling pathways. These results suggest that thyroid hormone status may influence ovarian function through cAMP-mediated mechanisms and highlight a potential link between thyroid dysfunction and altered reproductive endocrine regulation. Further studies are warranted to elucidate the underlying molecular pathways.