Localization of kisspeptin, NKB, and NK3R in the hypothalamus of gilts treated with the progestin altrenogest

Authors: LINDO, ASHLEY - West Virginia University; Thorson, Jennifer; BEDENBAUGH, MICHELLE - West Virginia University; MCCOSH, RICHARD - West Virginia University; LOPEZ, JUSTIN - West Virginia University; YOUNG, SAMANTHA - West Virginia University; MEADOWS, LANNY - West Virginia University; BOWDRIDGE, ELIZABETH - West Virginia University; FERGANI, CHRYSANTHI - University Of Mississippi Medical Center; Freking, Bradley - Brad; LEHMAN, MICHAEL - Kent State University; HILEMAN, STANLEY - West Virginia University; Lents, Clay

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/19/2021
Publication Date: 5/25/2021
Citation: Lindo, A.N., Thorson, J., Bedenbaugh, M.N., Mccosh, R.B., Lopez, J.A., Young, S.A., Meadows, L.J., Bowdridge, E.C., Fergani, C., Freking, B.A., Lehman, M.N., Hileman, S.M., Lents, C.A. 2021. Localization of kisspeptin, NKB, and NK3R in the hypothalamus of gilts treated with the progestin altrenogest. Biology of Reproduction. Article 103. https://doi.org/10.1093/biolre/ioab103.
DOI: https://doi.org/10.1093/biolre/ioab103

Interpretive Summary: Treating female pigs selected as replacement gilts with altrenogest is a common management practice in U.S. swine herds. Altrenogest suppress secretion of gonadotropin hormones that support development of follicles on the ovary, but exactly how this occurs is unknown. Scientists examined areas in the central nervous that regulate gonadotropin hormone secretion in gilts. They found that neurons in these areas expressed two neuropeptides called kisspeptin and neurokinin B and that these neuropeptides were mostly expressed in the same cells. Altrenogest treatment however did not affect how many cells expressed these important neuropeptides. Scientist also looked at receptors for these neuropeptides and found that cells expressing these receptors are in close contact with neurons controlling gonadotropin hormone secretion. These discoveries are an important step toward understanding how reproduction in the pig is controlled. Understand more about these mechanisms will be important for improving reproductive management of gilts.

Technical Abstract: Mechanisms in the brain controlling secretion of gonadotropin hormones in pigs, particularly luteinizing hormone (LH), are poorly understood. Kisspeptin is a potent LH stimulant that is essential for fertility in many species, including pigs. Neurokinin B (NKB) acting through neurokinin 3 receptor (NK3R) is involved in kisspeptin-stimulated LH release, but organization of NKB and NK3R within the porcine hypothalamus is unknown. Hypothalamic tissue from ovariectomized (OVX) gilts was used to determine the distribution of immunoreactive kisspeptin, NKB, and NK3R cells in the arcuate nucleus (ARC). Almost all kisspeptin neurons coexpressed NKB in the porcine ARC. Immunostaining for NK3R was distributed throughout the preoptic area (POA) and in several hypothalamic areas including the periventricular and retrochiasmatic areas but was not detected within the ARC. There was no colocalization of NK3R with gonadotropin-releasing hormone (GnRH), but NK3R-positive fibers in the POA were in close apposition to GnRH neurons. Treating OVX gilts with the progestin altrenogest decreased LH pulse frequency and reduced mean circulating concentrations of LH compared with OVX control gilts (P'<'0.01), but the number of kisspeptin and NKB cells in the ARC did not differ between treatments. The neuroanatomical arrangement of kisspeptin, NKB, and NK3R within the porcine hypothalamus confirm they are positioned to stimulate GnRH and LH secretion in gilts, though differences with other species exist. Altrenogest suppression of LH secretion in the OVX gilt does not appear to involve decreased peptide expression of kisspeptin or NKB.