Evidence for short-loop feedback effects of ACTH on CRF and vasopressin expression in parvocellular neurosecretory neurons.
Immuno- and hybridization histochemical methods were used to examine a possible role for adrenocorticotropic hormone (ACTH) in regulating the expression of corticotropin-releasing peptides in rat hypothalamus. Densitometric assessments of relative levels of mRNAs encoding corticotropin releasing factor (CRF), arginine vasopressin (AVP) and oxytocin (OT) in the parvocellular division of the paraventricular nucleus (PVH) were carried out in intact, adrenalectomized (ADX) and hypophysectomized (HYPOX) animals. Both surgeries resulted in comparable increases in relative levels of CRF and AVP transcripts in the parvocellular PVH; no effects on OT mRNA in this compartment were evident. In a second experiment, ACTH or saline vehicle were administered systemically via osmotic minipump for seven days to rats submitted to both HYPOX and ADX surgeries. Lower replacement doses of ACTH reduced the number of detectable AVP-immunoreactive (AVP-ir) cells in the parvocellular PVH to 53% of that seen in vehicle-treated HYPOX/ADX controls; the number of CRF-IR cells was not significantly affected. Higher doses of ACTH resulted in counts of AVP- and CRF-IR neurons that were reduced to 32% and 70%, respectively, of control values. Staining patterns for the two peptides in the external lamina of the median eminence generally followed the cell count data. Neither densitometric nor combined immunohistochemical (for CRF-ir) and hybridization histochemical (for AVP mRNA) assays revealed any marked effect of ACTH on AVP mRNA expression in the parvocellular PVH of HYPOX/ADX rats. The results indicate that ACTH is capable of inhibiting corticotropin-releasing peptide, but not mRNA, expression in hypophysiotropic neurons. The mechanisms underlying these effects remain to be fully clarified.
Salk Institute for Biological Studies, La Jolla 92186-5800, USA.
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Sawchenko
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Arias
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005246:Feedback / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000378:metabolism*
D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone