Does Dynorphin Play a Role in the Onset of Puberty in Female Sheep?
Puberty onset involves increased gonadotrophin-release (GnRH) release as a result of decreased sensitivity to oestrogen (E2)-negative feedback. Because GnRH neurones lack E2receptor α, this pathway must contain interneurones. One likely candidate is KNDy neurones (kisspeptin, neurokinin B, dynorphin). The overarching hypothesis of the present study was that the prepubertal hiatus in luteinising hormone (LH) release involves reduced kisspeptin and/or heightened dynorphin input. We first tested the specific hypothesis that E2would reduce kisspeptin-immunopositive cell numbers and increase dynorphin-immunopositive cell numbers. We found that kisspeptin cell numbers were higher in ovariectomised (OVX) lambs than OVX lambs treated with E2(OVX+ E2) or those left ovary-intact. Very few arcuate dynorphin cells were identified in any group. Next, we hypothesised that central blockade of κ-opioid receptor (KOR) would increase LH secretion at a prepubertal (6 months) but not postpubertal (10 months) age. Luteinising hormone pulse frequency and mean LH increased during infusion of a KOR antagonist, norbinaltorphimine, in OVX + E2lambs at the prepubertal age but not in the same lambs at the postpubertal age. We next hypothesised that E2would increase KOR expression in GnRH neurones or alter synaptic input to KNDy neurones in prepubertal ewes. Oestrogen treatment decreased the percentage of GnRH neurones coexpressing KOR (approximately 68%) compared to OVX alone (approximately 78%). No significant differences in synaptic contacts per cell between OVX and OVX + E2groups were observed. Although these initial data are consistent with dynorphin inhibiting pulsatile LH release prepubertally, additional work will be necessary to define the source and mechanisms of this inhibition.
Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA.
J A
JA
Lopez
Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA.
M N
MN
Bedenbaugh
Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA.
R B
RB
McCosh
Department of Neurobiology and Anatomical Sciences, The University of Mississippi Medical Center, Jackson, MS, USA.
P W
PW
Weems
Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA.
L J
LJ
Meadows
Department of Biology, Alderson-Broaddus University, Philippi, WV, USA.
B
B
Wisman
Department of Neurobiology and Anatomical Sciences, The University of Mississippi Medical Center, Jackson, MS, USA.
L M
LM
Coolen
Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA.
R L
RL
Goodman
Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA.
S M
SM
Hileman
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004399:Dynorphins / Q000502:physiology*; D004967:Estrogens / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D059648:Kisspeptins / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D011627:Puberty; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D034561:Sheep, Domestic; D016708:Synaptophysin / Q000378:metabolism
D004967:Estrogens; D059648:Kisspeptins; D017473:Receptors, Opioid, kappa; D016708:Synaptophysin; D007987:Gonadotropin-Releasing Hormone; D004399:Dynorphins; D007986:Luteinizing Hormone
GnRH; dynorphin; kappa opioid receptor; kisspeptin; ovine; puberty