Molecular diversity of corticotropin-releasing hormone mRNA-containing neurons in the hypothalamus

Roman A. Romanov, A. Alpár, Tomas Hokfelt, Tibor Harkany

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Hormonal responses to acute stress rely on the rapid induction of corticotropin-releasing hormone (CRH) production in the mammalian hypothalamus, with subsequent instructive steps culminating in corticosterone release at the periphery. Hypothalamic CRH neurons in the paraventricular nucleus of the hypothalamus are therefore considered as 'stress neurons'. However, significant morphological and functional diversity among neurons that can transiently produce CRH in other hypothalamic nuclei has been proposed, particularly as histochemical and molecular biology evidence associates CRH to both GABA and glutamate neurotransmission. Here, we review recent advances through single-cell RNA sequencing and circuit mapping to suggest that CRH production reflects a state switch in hypothalamic neurons and thus confers functional competence rather than being an identity mark of phenotypically segregated neurons. We show that CRH mRNA transcripts can therefore be seen in GABAergic, glutamatergic and dopaminergic neuronal contingents in the hypothalamus. We then distinguish 'stress neurons' of the paraventricular nucleus that constitutively express secretagogin, a Ca2+ sensor critical for the stimulus-driven assembly of the molecular machinery underpinning the fast regulated exocytosis of CRH at the median eminence. Cumulatively, we infer that CRH neurons are functionally and molecularly more diverse than previously thought.

Original languageEnglish
Pages (from-to)R161-R172
JournalJournal of Endocrinology
Volume232
Issue number3
DOIs
Publication statusPublished - 2017

Fingerprint

Corticotropin-Releasing Hormone
Hypothalamus
Neurons
Messenger RNA
Paraventricular Hypothalamic Nucleus
Pituitary Hormone-Releasing Hormones
RNA Sequence Analysis
Median Eminence
Exocytosis
Corticosterone
Synaptic Transmission
Mental Competency
gamma-Aminobutyric Acid
Molecular Biology
Glutamic Acid

Keywords

  • Calcium-binding proteins
  • Neuronal heterogeneity
  • Single-cell RNA-sequencing
  • Stress

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Molecular diversity of corticotropin-releasing hormone mRNA-containing neurons in the hypothalamus. / Romanov, Roman A.; Alpár, A.; Hokfelt, Tomas; Harkany, Tibor.

In: Journal of Endocrinology, Vol. 232, No. 3, 2017, p. R161-R172.

Research output: Contribution to journalArticle

Romanov, Roman A. ; Alpár, A. ; Hokfelt, Tomas ; Harkany, Tibor. / Molecular diversity of corticotropin-releasing hormone mRNA-containing neurons in the hypothalamus. In: Journal of Endocrinology. 2017 ; Vol. 232, No. 3. pp. R161-R172.
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