PMID- 21933866
OWN - NLM
STAT- MEDLINE
DCOM- 20111208
LR  - 20220410
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 152
IP  - 11
DP  - 2011 Nov
TI  - Developmental programming: reproductive endocrinopathies in the adult female 
      sheep after prenatal testosterone treatment are reflected in altered ontogeny of 
      GnRH afferents.
PG  - 4288-97
LID - 10.1210/en.2011-0117 [doi]
AB  - The GnRH system represents a useful model of long-term neural plasticity. An 
      unexplored facet of this plasticity relates to the ontogeny of GnRH neural 
      afferents during critical periods when the hypothalamic-pituitary-gonadal axis is 
      highly susceptible to perturbation by sex steroids. Sheep treated with 
      testosterone (T) in utero exhibit profound reproductive neuroendocrine 
      dysfunctions during their lifespan. The current study tested the hypothesis that 
      these changes are associated with alterations in the normal ontogeny of GnRH 
      afferents and glial associations. Adult pregnant sheep (n=50) were treated with 
      vehicle [control (CONT)] or T daily from gestational day (GD)30 to GD90. CONT and 
      T fetuses (n=4-6/treatment per age group) were removed by cesarean section on 
      GD90 and GD140 and the brains frozen at -80 degrees C. Brains were also collected from 
      CONT and T females at 20-23 wk (prepubertal), 10 months (normal onset of puberty 
      and oligo-anovulation), and 21 months (oligo-anovulation in T females). Tissue 
      was analyzed for GnRH immunoreactivity (ir), total GnRH afferents (Synapsin-I 
      ir), glutamate [vesicular glutamate transporter-2 (VGLUT2)-ir], and 
      gamma-aminobutyric acid [GABA, vesicular GABA transporter (VGAT)-ir] afferents and 
      glial associations (glial fibrillary acidic protein-ir) with GnRH neurons using 
      optical sectioning techniques. The results revealed that: 1) GnRH soma size was 
      slightly reduced by T, 2) the total (Synapsin-I) GnRH afferents onto both somas 
      and dendrites increased significantly with age and was reduced by T, 3) numbers 
      of both VGAT and VGLUT inputs increased significantly with age and were also 
      reduced by T, and 4) glial associations with GnRH neurons were reduced (<10%) by 
      T. Together, these findings reveal a previously unknown developmental plasticity 
      in the GnRH system of the sheep. The altered developmental trajectory of GnRH 
      afferents after T reinforces the notion that prenatal programming plays an 
      important role in the normal development of the reproductive neuroendocrine axis.
FAU - Jansen, Heiko T
AU  - Jansen HT
AD  - Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, 
      Washington State University, P.O. Box 646520, Pullman, Washington 99164-6520, 
      USA. heiko@vetmed.wsu.edu
FAU - Hershey, John
AU  - Hershey J
FAU - Mytinger, Andrea
AU  - Mytinger A
FAU - Foster, Douglas L
AU  - Foster DL
FAU - Padmanabhan, Vasantha
AU  - Padmanabhan V
LA  - eng
GR  - P01 HD044232/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110920
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Synapsins)
RN  - 0 (Vesicular Glutamate Transport Protein 2)
RN  - 0 (Vesicular Inhibitory Amino Acid Transport Proteins)
RN  - 0 (vesicular GABA transporter)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 3XMK78S47O (Testosterone)
SB  - IM
MH  - Animals
MH  - Estrous Cycle/physiology
MH  - Female
MH  - Gonadotropin-Releasing Hormone/*metabolism
MH  - Neuroglia/drug effects/metabolism
MH  - Neurons, Afferent/*drug effects/metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*metabolism
MH  - Reproduction/*drug effects
MH  - Sheep
MH  - Synapsins/metabolism
MH  - Testosterone/*pharmacology
MH  - Vesicular Glutamate Transport Protein 2/metabolism
MH  - Vesicular Inhibitory Amino Acid Transport Proteins/metabolism
PMC - PMC3199006
EDAT- 2011/09/22 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/11/01
CRDT- 2011/09/22 06:00
PHST- 2011/09/22 06:00 [entrez]
PHST- 2011/09/22 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - en.2011-0117 [pii]
AID - EN-11-0117 [pii]
AID - 10.1210/en.2011-0117 [doi]
PST - ppublish
SO  - Endocrinology. 2011 Nov;152(11):4288-97. doi: 10.1210/en.2011-0117. Epub 2011 Sep 
      20.