PMID- 7756451
OWN - NLM
STAT- MEDLINE
DCOM- 19950623
LR  - 20190512
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 52
IP  - 3
DP  - 1995 Mar
TI  - Neuromodulation of transplanted gonadotropin-releasing hormone neurons in male 
      and female hypogonadal mice with preoptic area brain grafts.
PG  - 572-83
AB  - Implantation of normal preoptic area (POA) tissue into the third ventricle of 
      adult hypogonadal (HPG) mice provides a source of GnRH neurons that innervate the 
      host median eminence and stimulate reproductive development in the sterile 
      mutants. To further evaluate graft-host integration, the effects of 
      N-methyl-D,L-aspartic acid (NMA) and opiate antagonists on LH secretion in HPG 
      mice with POA transplants (HPG/POA) were tested. NMA challenges significantly 
      stimulated LH secretion in 10 of 11 HPG/POA females. Only 5 of 12 HPG/POA males 
      responded to the same treatment. Administration of the opiate antagonists 
      naloxone or naloxone methiodide was ineffective in stimulating LH release in any 
      mice, but opiate antagonist pretreatment significantly potentiated the LH 
      secretory response to NMA in female, but not male, HPG/POA mice. A potential 
      anatomical substrate for this facilitation may be the 
      beta-endorphin-immunoreactive innervation of the POA grafts in all HPG/POA brains 
      examined. beta-Endorphin fibers were also present in the median eminence in the 
      vicinity of GnRH outgrowth from the grafts. However, similar innervation patterns 
      in HPG/POA males that did not respond to opioid antagonism suggests that this is 
      not sufficient. We tested whether the sex difference in HPG/POA responsivity to 
      neuromodulation is related to the steroid milieu in the hosts. 17 beta-Estradiol 
      (E2) treatment facilitated the LH secretory response of male HPG/POA to NMA 
      challenges whether animals were castrated and given an E2 capsule prior to graft 
      implantation or one week before testing two months after graft surgery. Intact or 
      vehicle (sesame oil)-treated, castrated HPG/POA males rarely responded to NMA 
      challenges, yet graft-derived GnRH innervation of the hosts' median eminence was 
      comparable in all treatment groups. GnRH challenge testing indicated that 
      pituitary sensitivity of the HPG/POA males was not significantly altered by E2 
      treatment, suggesting that estrogen acted centrally. These results indicate that 
      the activity of grafted GnRH neurons may be modulated by endogenous opioids of 
      host origin as well as by the hormonal milieu.
FAU - Miller, G M
AU  - Miller GM
AD  - Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, 
      USA.
FAU - Silverman, A J
AU  - Silverman AJ
FAU - Rogers, M C
AU  - Rogers MC
FAU - Gibson, M J
AU  - Gibson MJ
LA  - eng
GR  - HD19077/HD/NICHD NIH HHS/United States
GR  - NS20335/NS/NINDS NIH HHS/United States
GR  - T32DK07645/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Estrogens)
RN  - 0 (Narcotic Antagonists)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 9002-67-9 (Luteinizing Hormone)
SB  - IM
MH  - Animals
MH  - Brain Tissue Transplantation/*physiology
MH  - Cell Transplantation/*physiology
MH  - Estrogens/pharmacology
MH  - Female
MH  - Gonadotropin-Releasing Hormone/*biosynthesis
MH  - Hypogonadism/*physiopathology
MH  - Immunohistochemistry
MH  - Luteinizing Hormone/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - N-Methylaspartate/physiology
MH  - Narcotic Antagonists/pharmacology
MH  - *Nervous System Physiological Phenomena
MH  - Neurons/*physiology
MH  - Preoptic Area/*physiology
MH  - Sex Characteristics
EDAT- 1995/03/01 00:00
MHDA- 1995/03/01 00:01
CRDT- 1995/03/01 00:00
PHST- 1995/03/01 00:00 [pubmed]
PHST- 1995/03/01 00:01 [medline]
PHST- 1995/03/01 00:00 [entrez]
AID - 10.1095/biolreprod52.3.572 [doi]
PST - ppublish
SO  - Biol Reprod. 1995 Mar;52(3):572-83. doi: 10.1095/biolreprod52.3.572.