title: 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.
abstract: 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).
authors: Laboratory of Neurobiology and Behavior, Rockefeller University, New York, NY 10021, USA. ckrebs@umich.edu
authors: C J
authors: CJ
authors: Krebs
authors: D W
authors: DW
authors: Pfaff
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C434246:Scamp4 protein, rat; D011374:Progesterone