Kisspeptin has an independent and direct effect on the pituitary gland in the mare

Christianne Magee; Jason E Bruemmer; Kelly S Kirkley; Luke A Sylvester; Brittany Runyan; Terry M Nett; Edward L Squires; Colin M Clay

doi:10.1016/j.theriogenology.2020.07.031

Kisspeptin has an independent and direct effect on the pituitary gland in the mare

Theriogenology. 2020 Nov:157:199-209. doi: 10.1016/j.theriogenology.2020.07.031. Epub 2020 Jul 29.

Authors

Christianne Magee¹, Jason E Bruemmer², Kelly S Kirkley³, Luke A Sylvester⁴, Brittany Runyan⁵, Terry M Nett⁶, Edward L Squires⁷, Colin M Clay⁸

Affiliations

¹ Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO, USA; Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. Electronic address: Christianne.Magee@colostate.edu.
² Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO, USA; Department of Animal Sciences, College of Agricultural Sciences, Colorado State University, Fort Collins, CO, USA. Electronic address: jason.bruemmer@colostate.edu.
³ Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO, USA; Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. Electronic address: kelly.kirkley@colostate.edu.
⁴ Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO, USA; Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. Electronic address: luke.sylvester@rams.colostate.edu.
⁵ Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO, USA; Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. Electronic address: brittany.runyan@colostate.edu.
⁶ Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO, USA; Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. Electronic address: terry.nett@colostate.edu.
⁷ Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO, USA. Electronic address: edward.squires@uky.edu.
⁸ Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, CO, USA; Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. Electronic address: colin.clay@colostate.edu.

PMID: 32814247
DOI: 10.1016/j.theriogenology.2020.07.031

Abstract

To more clearly understand the equine gonadotrope response to kisspeptin and gonadotropin releasing hormone (GnRH), peripheral LH and FSH were quantified in diestrous mares after treatment with either equine kisspeptide (eKp-10, 0.5 mg iv), GnRH (25 μg iv), or a combination thereof every 4 h for 3 days. The following observations were made: 1) a diminished LH and FSH response to eKp-10 and GnRH was observed by Day 3, but was not different by treatment, 2) a decrease in basal LH concentration was observed from Day 1 to Day 3 for the eKp-10, but not the GnRH treated mares, 3) there was no change in basal FSH with either treatment. Additionally, pre-treatment with GnRH antagonist (antide 1.0 mg iv) eliminated any measurable change in LH after eKp-10 (1.0 mg iv) treatment. Both GnRH and kisspeptin are Gα_q/11 coupled receptors, therefore quantifying the rise in intracellular calcium following treatment with cognate ligand allows simultaneous assessment of receptor activation. Direct stimulation of equine primary pituitary cells with GnRH and/or eKp-10 demonstrates three distinct populations of pituitary cells: one population responded to both eKp-10 and GnRH, a second, independent population, responded to only eKp-10, and a third population responded only to GnRH. These populations were confirmed using co-immunofluorescence of hemipituitaries from mares in diestrus. Although the rise in peripheral LH concentration elicited by eKp-10 is dependent on GnRH, this work suggests that kisspeptin also has a specific and direct effect on the equine gonadotrope, independent of GnRH.

Keywords: Anterior pituitary; Equid (horse); GnRH; Kisspeptin.

MeSH terms

Animals
Female
Follicle Stimulating Hormone
Gonadotropin-Releasing Hormone / metabolism
Horses
Kisspeptins* / physiology
Luteinizing Hormone*
Pituitary Gland / metabolism

Substances

Kisspeptins
Gonadotropin-Releasing Hormone
Luteinizing Hormone
Follicle Stimulating Hormone