PMID- 25490143
OWN - NLM
STAT- MEDLINE
DCOM- 20150324
LR  - 20181202
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 156
IP  - 2
DP  - 2015 Feb
TI  - Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in 
      developing and adult rats.
PG  - 576-88
LID - 10.1210/en.2014-1026 [doi]
AB  - Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins 
      (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. 
      The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an 
      inhibitor, through kappa-opioid receptor) shape Kp secretion onto GnRH neurons. 
      However, some aspects of this paradigm remain ill defined. Here we aimed to 
      characterize the following: 1) the effects of NKB signaling on FSH secretion and 
      2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) 
      additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, 
      on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH 
      release were explored across postnatal development in male and female rats; 
      gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A 
      (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin 
      secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine 
      didydrochloride. Before puberty, rats of both sexes showed increased FSH 
      secretion to senktide (and Kp-10). Conversely, adult female rats were 
      irresponsive to senktide in terms of FSH, despite proven LH responses, whereas 
      the adult males did not display FSH or LH responses to senktide, even at high 
      doses. In turn, substance P and NKA stimulated gonadotropin secretion in 
      prepubertal rats, whereas in adults modest gonadotropin responses to NKA were 
      detected. By pretreatment with a Dyn antagonist, adult males became responsive to 
      senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; 
      nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide 
      in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and 
      kappa-opioid receptor, respectively) in the mediobasal hypothalamus was greater in 
      males than in females at prepubertal ages. Overall, our data contribute to 
      refining our understanding on how the elements of the KNDy node and related 
      factors (ie, other tachykinins) differentially participate in the control of 
      gonadotropins at different stages of rat postnatal maturation.
FAU - Ruiz-Pino, F
AU  - Ruiz-Pino F
AD  - Department of Cell Biology, Physiology, and Immunology (F.R.-P., D.G.-G., 
      M.M.-L., S.L., M.A.S.-G., J.R., L.P., M.T.-S.), University of Cordoba, and Centro 
      de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion 
      (F.R.-P., D.G.-G., J.R., L.P., M.T.-S.), and Instituto Maimonides de 
      Investigacion Biomedica de Cordoba/Hospital Universitario Reina Sofia (F.R.-P., 
      D.G.-G., J.R., L.P., M.T.-S.), 14004 Cordoba, Spain; and Division of 
      Endocrinology, Diabetes, and Hypertension (V.M.N.), Brigham and Women's Hospital 
      and Harvard Medical School, Boston, Massachusetts 02115.
FAU - Garcia-Galiano, D
AU  - Garcia-Galiano D
FAU - Manfredi-Lozano, M
AU  - Manfredi-Lozano M
FAU - Leon, S
AU  - Leon S
FAU - Sanchez-Garrido, M A
AU  - Sanchez-Garrido MA
FAU - Roa, J
AU  - Roa J
FAU - Pinilla, L
AU  - Pinilla L
FAU - Navarro, V M
AU  - Navarro VM
FAU - Tena-Sempere, M
AU  - Tena-Sempere M
LA  - eng
GR  - K99 HD071970/HD/NICHD NIH HHS/United States
GR  - R00 HD071970/HD/NICHD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141209
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Enkephalins)
RN  - 0 (Kisspeptins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protein Precursors)
RN  - 0 (Receptors, Neurokinin-1)
RN  - 0 (Receptors, Neurokinin-2)
RN  - 106128-89-6 (senktide)
RN  - 33507-63-0 (Substance P)
RN  - 74913-18-1 (Dynorphins)
RN  - 86933-75-7 (Neurokinin B)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - 93443-35-7 (preproenkephalin)
SB  - IM
MH  - Aging/*metabolism
MH  - Animals
MH  - Dynorphins/antagonists & inhibitors/metabolism
MH  - Enkephalins/metabolism
MH  - Female
MH  - Follicle Stimulating Hormone/*metabolism
MH  - Hypothalamus/metabolism
MH  - Kisspeptins/*metabolism
MH  - Luteinizing Hormone/*metabolism
MH  - Male
MH  - Neurokinin B/agonists/*metabolism
MH  - Peptide Fragments
MH  - Protein Precursors/metabolism
MH  - Rats, Wistar
MH  - Receptors, Neurokinin-1/agonists
MH  - Receptors, Neurokinin-2/agonists
MH  - Substance P/analogs & derivatives
PMC - PMC4298329
EDAT- 2014/12/10 06:00
MHDA- 2015/03/25 06:00
PMCR- 2016/02/01
CRDT- 2014/12/10 06:00
PHST- 2014/12/10 06:00 [entrez]
PHST- 2014/12/10 06:00 [pubmed]
PHST- 2015/03/25 06:00 [medline]
PHST- 2016/02/01 00:00 [pmc-release]
AID - EN-14-1026 [pii]
AID - 10.1210/en.2014-1026 [doi]
PST - ppublish
SO  - Endocrinology. 2015 Feb;156(2):576-88. doi: 10.1210/en.2014-1026. Epub 2014 Dec 
      9.