Altered Gene Expression Profiles of the Hypothalamic Arcuate Nucleus of Male Mice Suggest Profound Developmental Changes in Peptidergic Signaling.
Neuropeptides of the hypothalamic arcuate nucleus (ARC) regulate important homeostatic and endocrine functions and also play critical roles in pubertal development. The altered peptidergic and aminoacidergic neurotransmission accompanying pubertal maturation of the ARC is 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 14-day-old infantile and 60-day-old 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 was compared between the two time points. The adult animals showed increased mRNA levels encoding cocaine- and amphetamine-regulated transcripts, galanin-like peptide, dynorphin, kisspeptin, proopiomelanocortin, proenkephalin and galanin and a 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 increase (5-fold). Melanocortin receptor-3 and the Y1 and Y5 neuropeptide Y receptors increased 1.5- to 1.8-fold, whereas δ-opioid receptor and neurotensin receptor-1 transcripts were reduced by 27 and 21%, respectively. Androgen receptor, progesterone receptor and α-estrogen receptor transcripts increased by 54-72%. The mRNAs of glutamic acid decarboxylases-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 a reduced inhibitory and/or enhanced excitatory neuropeptidergic drive on fertility in adult animals.
Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Csilla S
CS
Molnár
Miklós
M
Sárvári
Csaba
C
Vastagh
Csilla
C
Maurnyi
Csaba
C
Fekete
Zsolt
Z
Liposits
Erik
E
Hrabovszky
D000367:Age Factors; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000254:growth & development* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics
D009479:Neuropeptides; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide