PMID- 26562263
OWN - NLM
STAT- MEDLINE
DCOM- 20160621
LR  - 20181202
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 157
IP  - 2
DP  - 2016 Feb
TI  - Both Estrogen and Androgen Modify the Response to Activation of Neurokinin-3 and 
      kappa-Opioid Receptors in Arcuate Kisspeptin Neurons From Male Mice.
PG  - 752-63
LID - 10.1210/en.2015-1688 [doi]
AB  - Gonadal steroids regulate the pattern of GnRH secretion. Arcuate kisspeptin 
      (kisspeptin, neurokinin B, and dynorphin [KNDy]) neurons may convey steroid 
      feedback to GnRH neurons. KNDy neurons increase action potential firing upon the 
      activation of neurokinin B receptors (neurokinin-3 receptor [NK3R]) and decrease 
      firing upon the activation of dynorphin receptors (kappa-opioid receptor [KOR]). In 
      KNDy neurons from intact vs castrated male mice, NK3R-mediated stimulation is 
      attenuated and KOR-mediated inhibition enhanced, suggesting gonadal secretions 
      are involved. Estradiol suppresses spontaneous GnRH neuron firing in male mice, 
      but the mediators of the effects on firing in KNDy neurons are unknown. We 
      hypothesized the same gonadal steroids affecting GnRH firing pattern would 
      regulate KNDy neuron response to NK3R and KOR agonists. To test this possibility, 
      extracellular recordings were made from KNDy neurons in brain slices from intact, 
      untreated castrated or castrated adult male mice treated in vivo with steroid 
      receptor agonists. As observed previously, the stimulation of KNDy neurons by the 
      NK3R agonist senktide was attenuated in intact vs castrated mice and suppression 
      by dynorphin was enhanced. In contrast to observations of steroid effects on the 
      GnRH neuron firing pattern, both estradiol and DHT suppressed senktide-induced 
      KNDy neuron firing and enhanced the inhibition caused by dynorphin. An estrogen 
      receptor-alpha agonist but not an estrogen receptor-beta agonist mimicked the effects of 
      estradiol on NK3R activation. These observations suggest the steroid modulation 
      of responses to activation of NK3R and KOR as mechanisms for negative feedback in 
      KNDy neurons and support the contribution of these neurons to steroid-sensitive 
      elements of a GnRH pulse generator.
FAU - Ruka, Kristen A
AU  - Ruka KA
AD  - Departments of Molecular and Integrative Physiology (K.A.R., L.L.B., S.M.M.), 
      Internal Medicine (S.M.M.), and Obstetrics and Gynecology (S.M.M.), University of 
      Michigan, Ann Arbor, Michigan 48109.
FAU - Burger, Laura L
AU  - Burger LL
AD  - Departments of Molecular and Integrative Physiology (K.A.R., L.L.B., S.M.M.), 
      Internal Medicine (S.M.M.), and Obstetrics and Gynecology (S.M.M.), University of 
      Michigan, Ann Arbor, Michigan 48109.
FAU - Moenter, Suzanne M
AU  - Moenter SM
AD  - Departments of Molecular and Integrative Physiology (K.A.R., L.L.B., S.M.M.), 
      Internal Medicine (S.M.M.), and Obstetrics and Gynecology (S.M.M.), University of 
      Michigan, Ann Arbor, Michigan 48109.
LA  - eng
GR  - R01 HD034860/HD/NICHD NIH HHS/United States
GR  - R01HD34860/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151112
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Androgens)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Estrogens)
RN  - 0 (Kisspeptins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Neurokinin-3)
RN  - 0 (Receptors, Opioid, kappa)
RN  - 0 (Receptors, Steroid)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 106128-89-6 (senktide)
RN  - 33507-63-0 (Substance P)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 4TI98Z838E (Estradiol)
RN  - 74913-18-1 (Dynorphins)
RN  - 86933-75-7 (Neurokinin B)
SB  - IM
MH  - Androgens/*pharmacology
MH  - Animals
MH  - Arcuate Nucleus of Hypothalamus
MH  - Dihydrotestosterone/*pharmacology
MH  - Dynorphins/metabolism
MH  - Estradiol/*pharmacology
MH  - Estrogen Receptor alpha/agonists
MH  - Estrogen Receptor beta/agonists
MH  - Estrogens/*pharmacology
MH  - Gonadotropin-Releasing Hormone
MH  - Kisspeptins/*metabolism
MH  - Male
MH  - Mice
MH  - Neurokinin B/metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Orchiectomy
MH  - Patch-Clamp Techniques
MH  - Peptide Fragments/pharmacology
MH  - Receptors, Neurokinin-3/*agonists
MH  - Receptors, Opioid, kappa/*agonists
MH  - Receptors, Steroid/agonists
MH  - Substance P/analogs & derivatives/pharmacology
PMC - PMC4733114
EDAT- 2015/11/13 06:00
MHDA- 2016/06/22 06:00
PMCR- 2017/02/01
CRDT- 2015/11/13 06:00
PHST- 2015/11/13 06:00 [entrez]
PHST- 2015/11/13 06:00 [pubmed]
PHST- 2016/06/22 06:00 [medline]
PHST- 2017/02/01 00:00 [pmc-release]
AID - EN-15-1688 [pii]
AID - 10.1210/en.2015-1688 [doi]
PST - ppublish
SO  - Endocrinology. 2016 Feb;157(2):752-63. doi: 10.1210/en.2015-1688. Epub 2015 Nov 
      12.