Expression of the SCAMP-4 gene, a new member of the secretory carrier membrane protein family, is repressed by progesterone in brain regions associated with female sexual behavior.
Rodent female reproductive behavior is facilitated by the genomic targets of estrogen (E) and progesterone (P) in neuroendocrine regions of the brain. Using the differential display-PCR technique to identify these targets we discovered a novel hormone-sensitive mRNA in the female rat brain that is substantially reduced in the ventromedial hypothalamus (VMH) after 3 h of P treatment, following 24 h of E priming. Northern blots show that it is a single transcript of approximately 1.7 kb. The sequence of the corresponding full-length cDNA indicates that this gene is the rat homolog of mouse SCAMP-4, the fourth member identified in a family of proteins known as secretory carrier membrane proteins (SCAMPs). In situ hybridization studies show that SCAMP-4 mRNA is relatively low throughout the rat forebrain, with the highest levels observed in the VMH, habenula and hippocampus. The SCAMP-4 message is also less abundant in the habenula and VMH during proestrus, when circulating levels of E and P are at their peak, than during diestrus-1 when circulating hormone levels are low. Amino acid sequence analysis indicates that SCAMP-4 lacks the putative calcium binding and leucine zipper structures, as well as protein-protein interacting NPF domains common among most SCAMP family members, but is the only member identified to date to contain a putative protein kinase C (PKC) phosphorylation site. Fluorescent microscopy of cells transfected with a SCAMP-4/GFP fusion construct reveals distinct fluorescence in subcellular aggregates that may contain secretory vesicles. In addition to our results in the VMH, the finding of high levels of SCAMP-4 message in the habenula, a brain area rich in mast cells, together with previous reports linking mast cell secretion with courtship behavior also suggest a possible role for SCAMP-4 in reproductive behaviors associated with mast cell activity in the central nervous system (CNS).
Krebs
C J
CJ
Laboratory of Neurobiology and Behavior, Rockefeller University, New York, NY 10021, USA. ckrebs@umich.edu
Pfaff
D W
DW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000032:analysis; D004031:Diestrus / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D010052:Ovariectomy; D010902:Pituitary Gland / Q000737:chemistry / Q000502:physiology; D011187:Posture / Q000502:physiology; D011359:Proestrus / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000737:chemistry / Q000502:physiology; D012726:Sexual Behavior, Animal / Q000502:physiology*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C434246:Scamp4 protein, rat; D011374:Progesterone