title: Evidence That Endogenous Somatostatin Inhibits Episodic, but Not Surge, Secretion of LH in Female Sheep.
abstract: Two modes of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion are necessary for female fertility: surge and episodic secretion. However, the neural systems that regulate these GnRH secretion patterns are still under investigation. The neuropeptide somatostatin (SST) inhibits episodic LH secretion in humans and sheep, and several lines of evidence suggest SST may regulate secretion during the LH surge. In this study, we examined whether SST alters the LH surge in ewes by administering a SST receptor (SSTR) 2 agonist (octreotide) or antagonist [CYN154806 (CYN)] into the third ventricle during an estrogen-induced LH surge and whether endogenous SST alters episodic LH secretion. Neither octreotide nor CYN altered the amplitude or timing of the LH surge. Administration of CYN to intact ewes during the breeding season or anestrus increased LH secretion and increased c-Fos in a subset GnRH and kisspeptin cells during anestrus. To determine if these stimulatory effects are steroid dependent or independent, we administered CYN to ovariectomized ewes. This SSTR2 antagonist increased LH pulse frequency in ovariectomized ewes during anestrus but not during the breeding season. This study provides evidence that endogenous SST contributes to the control of LH secretion. The results demonstrate that SST, acting through SSTR2, inhibits episodic LH secretion, likely acting in the mediobasal hypothalamus, but action at this receptor does not alter surge secretion. Additionally, these data provide evidence that SST contributes to the steroid-independent suppression of LH pulse frequency during anestrus.
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Richard B
authors.initials: RB
authors.lastname: McCosh
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Szeligo
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Bedenbaugh
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Lopez
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Hardy
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Hileman
authors.affiliation: Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi 39216.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Lehman
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Goodman
mesh_terms: D000780:Anestrus / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D015282:Octreotide / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010052:Ovariectomy; D055571:Secretory Pathway / Q000187:drug effects; D012756:Sheep; D013004:Somatostatin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C403089:CYN 154806; D009842:Oligopeptides; D004958:Estradiol; D013004:Somatostatin; D007986:Luteinizing Hormone; D015282:Octreotide