Putative role of cocaine- and amphetamine-regulated transcript (CARTPT) in dominant follicle selection in cattle

The mechanisms regulating development of a single (dominant) follicle capable of ovulation during each follicular wave in cattle and atresia of remaining follicles (dominant follicle selection) are not well understood. FSH and IGF1 are known regulators of follicle growth and granulosa cell estradiol production during follicular waves. Recent evidence indicates cocaine and amphetamine regulated transcript (CARTPT), with intraovarian expression only in single-ovulating species, is a novel regulator of follicular development. The mature CARTPT peptide (CART) is a potent negative regulator of FSH and IGF1 action on granulosa cells in vitro and can inhibit follicular estradiol production in vivo. Follicular fluid CART concentrations in healthy follicles decrease after dominant follicle selection and CARTPT mRNA is lower in healthy versus atretic follicles collected prior to and early after initiation of follicle dominance, suggestive of a regulatory role in the selection process. The inhibitory actions of CART on FSH signaling and estradiol production are dependent on the G(o/i)-subclass of inhibitory G proteins and linked to multiple components of the FSH signal transduction pathway resulting in reduced CYP19A1 mRNA and estradiol production. Evidence to date supports a potential important functional role for CART in regulation of dominant follicle selection and the species-specific ovulatory quota in monotocous species.