The pituitary gonadotropin, luteinizing hormone (LH), plays a central role in reproductive function. In Old World primates, LH stimulates ovulation in females and testosterone production in males. LH is upregulated and released upon gonadotropin releasing hormone (GnRH) stimulation and is stored with secretogranin II (SgII), a granin that may play a role in the sorting of LH to dense core vesicles of the regulated secretion pathway.

Recent studies have found that squirrel monkeys and other New World primates lack expression of LH in the pituitary. Instead, chorionic gonadotropin (CG), normally expressed in the placenta of Old World primates, is the active luteotropic pituitary hormone in New World primates. Therefore, CG is expressed both in the pituitary and the placenta of these animals. In order for CG to take the place of LH in these animals, it must be regulated in a way that allows for controlled response to GnRH stimulation. The objective of this project was to investigate the pituitary-specific regulation and storage of CG in a New World primate, the squirrel monkey. The first goal of the study was to isolate the squirrel monkey CGβ promoter and identify cis-elements necessary for pituitary-specific regulation. Mutations of the squirrel monkey CGβ promoter showed that pituitary-specific GnRH-responsiveness is governed by Egr-1 binding sites in the proximal 250 bp of the promoter. Placenta-specific expression, on the other hand, is mediated by distinct cis-elements found further upstream. Second, the role that SgII plays in the storage of squirrel monkey CG in the pituitary was investigated. The squirrel monkey CGβ and SgII promoters are not only coregulated by GnRH in reporter gene assays, but also colocalize in squirrel monkey pituitary. However, SgII may not play an essential role in the aggregation of CG into dense core vesicles, as CG can form granules in the absence of SgII in COS-7 cells. These data provide insight into the mechanisms by which New World primate CG expression and storage is differentially regulated in a pituitary- and placenta-specific manner and add to the larger picture of gonadotropin regulation and storage.