Cell-type-specific localization of huntingtin-associated protein 1 in neuroendocrine and neurosecretory systems of the mouse hypothalamic–pituitary axis

Huntingtin-associated protein 1 (HAP1) is a neurocytoplasmic protein implicated in intracellular trafficking, vesicular transport, and neuroprotection. Although HAP1 is abundantly expressed in hypothalamic regions involved in neuroendocrine regulation, its distribution and cellular specificity within the hypothalamic–pituitary axis remain poorly understood. Therefore, the present study aimed to characterize the expression pattern and cellular localization of HAP1 in neuroendocrine and neurosecretory systems of the adult mouse hypothalamic–pituitary axis. Adult male C57BL/6 J mice were analyzed using Western blotting, single-label immunoperoxidase histochemistry, and double-label immunofluorescence immunohistochemistry combined with hormone-specific markers. HAP1 immunoreactivity was detected throughout the pituitary gland, showing moderate scattered labeling in the anterior lobe, diffuse expression in the intermediate lobe, and intense accumulation in the posterior lobe. In the anterior and intermediate pituitary, HAP1 was highly expressed in thyrotrophs, corticotrophs, and melanotrophs, whereas gonadotrophs exhibited relatively low expression. In contrast, somatotrophs and lactotrophs lacked detectable HAP1 immunoreactivity. In the posterior pituitary, HAP1 was absent from S100β-positive pituicytes but strongly co-localized with oxytocin (OXT)- and arginine vasopressin (AVP)-containing neurosecretory structures, putative herring bodies. In the hypothalamus, HAP1 was prominently expressed in magnocellular neurons of the paraventricular and supraoptic nuclei and extensively co-localized with OXT- and AVP-producing neurons. Collectively, these findings demonstrate a highly cell-type-specific and compartmentalized distribution of HAP1 across the hypothalamic–pituitary axis. The continuous localization of HAP1 from hypothalamic neuronal somata to neurosecretory terminals provides an anatomical basis for investigating potential roles in vesicular trafficking, neuropeptide transport, and neurosecretory regulation, as well as its possible contribution to selective cellular resilience within neuroendocrine systems.