title: Regulation of granulosa cell cocaine and amphetamine regulated transcript (CART) binding and effect of CART signaling inhibitor on granulosa cell estradiol production during dominant follicle selection in cattle.
abstract: We previously established a potential role for cocaine and amphetamine regulated transcript (CARTPT) in dominant follicle selection in cattle. CARTPT expression is elevated in subordinate versus dominant follicles, and treatment with the mature form of the CARTPT peptide (CART) decreases follicle-stimulating hormone (FSH)-stimulated granulosa cell estradiol production in vitro and follicular fluid estradiol and granulosa cell CYP19A1 mRNA in vivo. However, mechanisms that regulate granulosa cell CART responsiveness are not understood. In this study, we investigated hormonal regulation of granulosa cell CART-binding sites in vitro and temporal regulation of granulosa cell CART-binding sites in bovine follicles collected at specific stages of a follicular wave. We also determined the effect of inhibition of CART receptor signaling in vivo on estradiol production in future subordinate follicles. Granulosa cell CART binding in vitro was increased by FSH, and this induction was blocked by estrogen receptor antagonist treatment. In follicles collected in vivo at specific stages of a follicular wave, granulosa cell CART binding in the F2 (second largest), future subordinate follicle increased during dominant follicle selection. Injection into the F2 follicle (at onset of diameter deviation) of an inhibitor of the o/i subclass of G proteins (previously shown to block CART actions in vitro) resulted in increased follicular fluid estradiol concentrations in vivo. Collectively, results demonstrate hormonal regulation of granulosa cell CART binding in vitro and temporal regulation of CART binding in subordinate follicles during dominant follicle selection. Results also suggest that CART signaling may help suppress estradiol-producing capacity of the F2 (subordinate) follicle during this time period.
authors.affiliation: Laboratory of Mammalian Reproductive Biology and Genomics, Michigan State University, East Lansing, Michigan.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Folger
authors.forename: Fermin
authors.initials: F
authors.lastname: Jimenez-Krassel
authors.forename: James J
authors.initials: JJ
authors.lastname: Ireland
authors.forename: Lihua
authors.initials: L
authors.lastname: Lv
authors.forename: George W
authors.initials: GW
authors.lastname: Smith
mesh_terms: D000818:Animals; D002417:Cattle; D048429:Cell Size / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D000077267:Fulvestrant; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009866:Oogenesis / Q000187:drug effects; D006080:Ovarian Follicle / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013498:Suramin / Q000031:analogs & derivatives / Q000494:pharmacology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D004965:Estrogen Antagonists; C105374:NF023; D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000077267:Fulvestrant; D004958:Estradiol; D013498:Suramin; D005640:Follicle Stimulating Hormone
keywords: atresia; bovine; cocaine and amphetamine regulated transcript (CART); estradiol/estradiol receptor; follicular development; granulosa cell; ovary