PMID- 32005991 OWN - NLM STAT- MEDLINE DCOM- 20200731 LR - 20240423 IS - 1945-7170 (Electronic) IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 161 IP - 4 DP - 2020 Apr 1 TI - Role for Kisspeptin and Neurokinin B in Regulation of Luteinizing Hormone and Testosterone Secretion in the Fetal Sheep. LID - 10.1210/endocr/bqaa013 [doi] LID - bqaa013 AB - Evidence suggests that the hypothalamic-pituitary-gonadal (HPG) axis is active during the critical period for sexual differentiation of the ovine sexually dimorphic nucleus, which occurs between gestational day (GD) 60 and 90. Two possible neuropeptides that could activate the fetal HPG axis are kisspeptin and neurokinin B (NKB). We used GD85 fetal lambs to determine whether intravenous administration of kisspeptin-10 (KP-10) or senktide (NKB agonist) could elicit luteinizing hormone (LH) release. Immunohistochemistry and fluorescent in situ hybridization (FISH) were employed to localize these peptides in brains of GD60 and GD85 lamb fetuses. In anesthetized fetuses, KP-10 elicited robust release of LH that was accompanied by a delayed rise in serum testosterone in males. Pretreatment with the GnRH receptor antagonist (acyline) abolished the LH response to KP-10, confirming a hypothalamic site of action. In unanesthetized fetuses, senktide, as well as KP-10, elicited LH release. The senktide response of females was greater than that of males, indicating a difference in NKB sensitivity between sexes. Gonadotropin-releasing hormone also induced a greater LH discharge in females than in males, indicating that testosterone negative feedback is mediated through pituitary gonadotrophs. Kisspeptin and NKB immunoreactive cells in the arcuate nucleus were more abundant in females than in males. Greater than 85% of arcuate kisspeptin cells costained for NKB. FISH revealed that the majority of these were kisspeptin/NKB/dynorphin (KNDy) neurons. These results support the hypothesis that kisspeptin-GnRH signaling regulates the reproductive axis of the ovine fetus during the prenatal critical period acting to maintain a stable androgen milieu necessary for brain masculinization. CI - (c) Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Amodei, Rebecka AU - Amodei R AD - Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon. FAU - Gribbin, Kyle AU - Gribbin K AD - Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon. FAU - He, Wen AU - He W AD - Brain Health Research Institute, Kent State University, Kent, Ohio. AD - Department of Biological Sciences, Kent State University, Kent, Ohio. FAU - Lindgren, Isa AU - Lindgren I AD - Center for Developmental Health, Oregon Health and Science University, Portland, Oregon. FAU - Corder, Keely R AU - Corder KR AD - Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, Oregon. FAU - Jonker, Sonnet S AU - Jonker SS AD - Center for Developmental Health, Oregon Health and Science University, Portland, Oregon. FAU - Estill, Charles T AU - Estill CT AD - Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, Oregon. AD - College of Veterinary Medicine, Oregon State University, Corvallis, Oregon. FAU - Coolen, Lique M AU - Coolen LM AD - Brain Health Research Institute, Kent State University, Kent, Ohio. AD - Department of Biological Sciences, Kent State University, Kent, Ohio. FAU - Lehman, Michael N AU - Lehman MN AD - Brain Health Research Institute, Kent State University, Kent, Ohio. AD - Department of Biological Sciences, Kent State University, Kent, Ohio. FAU - Whitler, William AU - Whitler W AD - College of Veterinary Medicine, Oregon State University, Corvallis, Oregon. FAU - Stormshak, Fred AU - Stormshak F AD - Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, Oregon. FAU - Roselli, Charles E AU - Roselli CE AD - Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon. LA - eng GR - R01 OD011047/OD/NIH HHS/United States GR - P51 OD011092/OD/NIH HHS/United States GR - P01 HD034430/HD/NICHD NIH HHS/United States GR - R01 HD039916/HD/NICHD NIH HHS/United States GR - P30 NS061800/NS/NINDS NIH HHS/United States GR - R01 HL142483/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (KISS1 protein, human) RN - 0 (Kisspeptins) RN - 0 (Oligopeptides) RN - 0 (Peptide Fragments) RN - 0 (Receptors, Kisspeptin-1) RN - 0 (Receptors, Neurokinin-3) RN - 106128-89-6 (senktide) RN - 33507-63-0 (Substance P) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - 3XMK78S47O (Testosterone) RN - 86933-75-7 (Neurokinin B) RN - 9002-67-9 (Luteinizing Hormone) RN - S3439D3B35 (acyline) SB - IM MH - Animals MH - Female MH - Fetus MH - Gonadotropin-Releasing Hormone/pharmacology MH - Hypothalamus/*drug effects/metabolism MH - Kisspeptins/metabolism/*pharmacology MH - Luteinizing Hormone/*blood MH - Male MH - Neurokinin B/metabolism MH - Oligopeptides/pharmacology MH - Peptide Fragments/pharmacology MH - Pregnancy MH - Receptors, Kisspeptin-1/agonists MH - Receptors, Neurokinin-3/agonists MH - Sheep MH - Substance P/analogs & derivatives/pharmacology MH - Testosterone/*blood PMC - PMC7079722 OTO - NOTNLM OT - Kisspeptin OT - fetal sheep OT - luteinizing hormone OT - neurokinin B OT - testosterone EDAT- 2020/02/02 06:00 MHDA- 2020/08/01 06:00 PMCR- 2021/02/01 CRDT- 2020/02/02 06:00 PHST- 2019/12/20 00:00 [received] PHST- 2020/01/29 00:00 [accepted] PHST- 2020/02/02 06:00 [pubmed] PHST- 2020/08/01 06:00 [medline] PHST- 2020/02/02 06:00 [entrez] PHST- 2021/02/01 00:00 [pmc-release] AID - 5719546 [pii] AID - bqaa013 [pii] AID - 10.1210/endocr/bqaa013 [doi] PST - ppublish SO - Endocrinology. 2020 Apr 1;161(4):bqaa013. doi: 10.1210/endocr/bqaa013.