Premium
A secretagogin locus of the mammalian hypothalamus controls stress hormone release
Author(s) -
Romanov Roman A,
Alpár Alán,
Zhang MingDong,
Zeisel Amit,
Calas André,
Landry Marc,
Fuszard Matthew,
Shirran Sally L,
Schnell Robert,
Dobolyi Árpád,
Oláh Márk,
Spence Lauren,
Mulder Jan,
Martens Henrik,
Palkovits Miklós,
Uhlen Mathias,
Sitte Harald H,
Botting Catherine H,
Wagner Ludwig,
Linnarsson Sten,
Hökfelt Tomas,
Harkany Tibor
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201488977
Subject(s) - biology , hypothalamus , locus (genetics) , hormone , endocrinology , medicine , genetics , gene
A hierarchical hormonal cascade along the hypothalamic‐pituitary‐adrenal axis orchestrates bodily responses to stress. Although corticotropin‐releasing hormone ( CRH ), produced by parvocellular neurons of the hypothalamic paraventricular nucleus ( PVN ) and released into the portal circulation at the median eminence, is known to prime downstream hormone release, the molecular mechanism regulating phasic CRH release remains poorly understood. Here, we find a cohort of parvocellular cells interspersed with magnocellular PVN neurons expressing secretagogin. Single‐cell transcriptome analysis combined with protein interactome profiling identifies secretagogin neurons as a distinct CRH ‐releasing neuron population reliant on secretagogin's Ca 2+ sensor properties and protein interactions with the vesicular traffic and exocytosis release machineries to liberate this key hypothalamic releasing hormone. Pharmacological tools combined with RNA interference demonstrate that secretagogin's loss of function occludes adrenocorticotropic hormone release from the pituitary and lowers peripheral corticosterone levels in response to acute stress. Cumulatively, these data define a novel secretagogin neuronal locus and molecular axis underpinning stress responsiveness.