Altered Gene Expression Profile of the Hypothalamic Arcuate Nucleus of Male Mice Suggests Profound Developmental Changes in Peptidergic Signaling

Csilla S. Molnár, Miklós Sárvári, Csaba Vastagh, Csilla Maurnyi, Csaba Fekete, Z. Liposits, E. Hrabovszky

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Neuropeptides of the hypothalamic arcuate nucleus (ARC) regulate important homeostatic and endocrine functions and also play critical roles in pubertal development. Altered peptidergic and amino acidergic neurotransmission accompanying pubertal maturation of the ARC are not fully understood. Here we studied the developmental shift in the gene expression profile of the ARC of male mice. RNA samples for quantitative RT-PCR studies were isolated from the ARC of day-14 infantile and day-60 adult male mice with laser-capture microdissection. The expression of 18 neuropeptide-, 15 neuropeptide receptor-, 4 sex steroid receptor and 6 classic neurotransmitter marker mRNAs were compared between the two timepoints. Adult animals showed increased mRNA levels encoding cocaine- and amphetamine-regulated transcript, galanin-like peptide, dynorphin, kisspeptin, proopiomelanocortin, proenkephalin and galanin and reduced expression of mRNAs for pituitary adenylate cyclase activating peptide, calcitonin gene-related peptide, neuropeptide Y, substance P, agouti-related protein, neurotensin and growth hormone-releasing hormone. From the neuropeptide receptors tested, melanocortin receptor-4 showed the most striking (5-fold) increase. Melanocortin receptor-3 and the Y1 and Y5 neuropeptide Y receptors increased 1.5-1.8-fold, whereas δ-opioid receptor and neurotensin receptor-1 transcripts were reduced by 27 and 21%, respectively. Androgen-, progesterone- and α-estrogen receptor transcripts increased by 54-72%. The mRNAs of glutamic acid decarboxylase 65, and 67, vesicular GABA transporter and choline acetyltransferase remained unchanged. Tyrosine hydroxylase mRNA increased by 44%, whereas type-2 vesicular glutamate transporter mRNA decreased by 43% by adulthood. Many of the developmental changes we revealed in this study suggest reduced inhibitory and/or enhanced excitatory neuropeptidergic drive on fertility in adult animals.

Original languageEnglish
JournalNeuroendocrinology
DOIs
Publication statusAccepted/In press - Aug 25 2015

Fingerprint

Arcuate Nucleus of Hypothalamus
Transcriptome
Messenger RNA
Neuropeptide Receptors
Neuropeptides
Galanin-Like Peptide
Vesicular Glutamate Transport Protein 2
Receptor, Melanocortin, Type 3
Agouti-Related Protein
Kisspeptins
Receptor, Melanocortin, Type 4
Laser Capture Microdissection
Galanin
Dynorphins
Growth Hormone-Releasing Hormone
Pro-Opiomelanocortin
Neurotensin
Glutamate Decarboxylase
Choline O-Acetyltransferase
Calcitonin Gene-Related Peptide

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Altered Gene Expression Profile of the Hypothalamic Arcuate Nucleus of Male Mice Suggests Profound Developmental Changes in Peptidergic Signaling. / Molnár, Csilla S.; Sárvári, Miklós; Vastagh, Csaba; Maurnyi, Csilla; Fekete, Csaba; Liposits, Z.; Hrabovszky, E.

In: Neuroendocrinology, 25.08.2015.

Research output: Contribution to journalArticle

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abstract = "Neuropeptides of the hypothalamic arcuate nucleus (ARC) regulate important homeostatic and endocrine functions and also play critical roles in pubertal development. Altered peptidergic and amino acidergic neurotransmission accompanying pubertal maturation of the ARC are not fully understood. Here we studied the developmental shift in the gene expression profile of the ARC of male mice. RNA samples for quantitative RT-PCR studies were isolated from the ARC of day-14 infantile and day-60 adult male mice with laser-capture microdissection. The expression of 18 neuropeptide-, 15 neuropeptide receptor-, 4 sex steroid receptor and 6 classic neurotransmitter marker mRNAs were compared between the two timepoints. Adult animals showed increased mRNA levels encoding cocaine- and amphetamine-regulated transcript, galanin-like peptide, dynorphin, kisspeptin, proopiomelanocortin, proenkephalin and galanin and reduced expression of mRNAs for pituitary adenylate cyclase activating peptide, calcitonin gene-related peptide, neuropeptide Y, substance P, agouti-related protein, neurotensin and growth hormone-releasing hormone. From the neuropeptide receptors tested, melanocortin receptor-4 showed the most striking (5-fold) increase. Melanocortin receptor-3 and the Y1 and Y5 neuropeptide Y receptors increased 1.5-1.8-fold, whereas δ-opioid receptor and neurotensin receptor-1 transcripts were reduced by 27 and 21{\%}, respectively. Androgen-, progesterone- and α-estrogen receptor transcripts increased by 54-72{\%}. The mRNAs of glutamic acid decarboxylase 65, and 67, vesicular GABA transporter and choline acetyltransferase remained unchanged. Tyrosine hydroxylase mRNA increased by 44{\%}, whereas type-2 vesicular glutamate transporter mRNA decreased by 43{\%} by adulthood. Many of the developmental changes we revealed in this study suggest reduced inhibitory and/or enhanced excitatory neuropeptidergic drive on fertility in adult animals.",
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AU - Liposits, Z.

AU - Hrabovszky, E.

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