Anterior pituitary hormone secretion is generally considered to be under the strong regulation of hypothalamic neuropeptides. In mammals, adrenocorticotropic hormone (ACTH), which plays a crucial role in the stress response, is secreted from corticotropes and is regulated primarily by corticotropin-releasing hormone (CRH). In teleosts, although the pharmacological effects of hypothalamic factors have been demonstrated, their relative importance in regulating ACTH release remains controversial. One reason for this is the lack of methods for evaluating ACTH release at cellular resolution. Using medaka as a model organism, we systematically examined the direct effects of hypothalamic peptides on ACTH cells by combining cell type-specific transcriptomics with Ca²⁺ imaging. We show that thyrotropin-releasing hormone (TRH) robustly elevates intracellular Ca²⁺ (Ca²⁺ᵢ) levels in ACTH cells, surpassing the responses elicited by CRH or arginine vasotocin (AVT). TRH also strongly activates MSH cells, the other POMC-derived pituitary cell population, while CRH induces only a modest response. Furthermore, in situ hybridization chain reaction analyses revealed that TRH receptor (trhra) is expressed in MSH cells, supporting their direct responsiveness to TRH signaling, whereas TRH receptor expression in ACTH cells was below thsse detection limit, leaving open the possibility that their activation is mediated by indirect or low-abundance receptor pathways. These findings suggest the existence of a novel TRH-driven regulatory pathway orchestrating both the teleost stress axis and pigmentation axis.
Yamakawa et al. (Sat,) studied this question.