PMID- 25216387
OWN - NLM
STAT- MEDLINE
DCOM- 20150708
LR  - 20240324
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 155
IP  - 12
DP  - 2014 Dec
TI  - Prenatal influence of an androgen agonist and antagonist on the differentiation 
      of the ovine sexually dimorphic nucleus in male and female lamb fetuses.
PG  - 5000-10
LID - 10.1210/en.2013-2176 [doi]
AB  - The ovine sexually dimorphic nucleus (oSDN) is 2 times larger in rams than in 
      ewes. Sexual differentiation of the oSDN is produced by testosterone exposure 
      during the critical period occurring between gestational day (GD)60 and GD90 
      (term, 147 d). We tested the hypothesis that testosterone acts through the 
      androgen receptor to control development of the male-typical oSDN. In experiment 
      1, pregnant ewes received injections of vehicle, androgen receptor antagonist 
      flutamide, or nonaromatizable androgen dihydrotestosterone (DHT) propionate 
      during the critical period. Fetuses were delivered at GD135. Both antagonist and 
      agonist treatments significantly reduced mean oSDN volume in males but had no 
      effects in females. Experiment 2, we analyzed the effect of treatments on the 
      fetal hypothalamic-pituitary-gonadal axis to determine whether compensatory 
      changes in hormone secretion occurred that could explain the effect of DHT. 
      Pregnant ewes were injected with vehicle, flutamide, or DHT propionate from GD60 
      to GD84, and fetuses were delivered on GD85. Flutamide significantly increased LH 
      and testosterone in males, whereas DHT significantly decreased both hormones. In 
      females, LH was unaffected by flutamide but significantly reduced by DHT 
      exposure. DHT significantly decreased pituitary gonadotropin and hypothalamic 
      kisspeptin mRNA expression in males and females. These results suggest that 
      androgen receptor mediates the effect of testosterone on oSDN masculinization, 
      because this process was blocked by the androgen receptor antagonist flutamide in 
      eugonadal males. In contrast, the reduction of oSDN volume observed after DHT 
      exposure appears to be mediated by a negative feedback mechanism exerted on the 
      hypothalamus to reduce LH and testosterone secretion. The reduced androgen 
      exposure most likely accounted for the decreased oSDN volume. We conclude that, 
      during the critical period, the male reproductive axis in long gestation species, 
      such as sheep, is sufficiently developed to react to perturbations in serum 
      androgens and mitigate disruptions in brain masculinization.
FAU - Roselli, Charles E
AU  - Roselli CE
AD  - Department of Physiology and Pharmacology (C.E.R., R.C.R., M.S.), Oregon Health 
      and Science University, Portland, Oregon 97239-3098; and Departments of Animal 
      and Rangeland Sciences (C.T.E., M.M., F.S.) and Clinical Sciences (C.T.E., 
      H.J.M.), College of Veterinary Medicine, Oregon State University, Corvallis, 
      Oregon 97331-4501.
FAU - Reddy, Radhika C
AU  - Reddy RC
FAU - Estill, Charles T
AU  - Estill CT
FAU - Scheldrup, Melissa
AU  - Scheldrup M
FAU - Meaker, Mary
AU  - Meaker M
FAU - Stormshak, Fred
AU  - Stormshak F
FAU - Montilla, Hernan J
AU  - Montilla HJ
LA  - eng
GR  - P51 OD011092/OD/NIH HHS/United States
GR  - R01 OD011047/OD/NIH HHS/United States
GR  - R01OD011047/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140912
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Androgen Antagonists)
RN  - 0 (Androgens)
RN  - 0 (Kisspeptins)
RN  - 0 (Receptors, Androgen)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 3XMK78S47O (Testosterone)
RN  - 76W6J0943E (Flutamide)
RN  - 9002-67-9 (Luteinizing Hormone)
SB  - IM
MH  - Androgen Antagonists
MH  - Androgens
MH  - Animals
MH  - Dihydrotestosterone
MH  - Female
MH  - Flutamide
MH  - Hypothalamo-Hypophyseal System/metabolism
MH  - Kisspeptins/metabolism
MH  - Luteinizing Hormone/blood
MH  - Male
MH  - Pregnancy
MH  - Preoptic Area/*embryology
MH  - Receptors, Androgen/*metabolism
MH  - *Sex Characteristics
MH  - Sheep
MH  - Testosterone/*metabolism
PMC - PMC4239424
EDAT- 2014/09/13 06:00
MHDA- 2015/07/15 06:00
PMCR- 2015/12/01
CRDT- 2014/09/13 06:00
PHST- 2014/09/13 06:00 [entrez]
PHST- 2014/09/13 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - EN-13-2176 [pii]
AID - 10.1210/en.2013-2176 [doi]
PST - ppublish
SO  - Endocrinology. 2014 Dec;155(12):5000-10. doi: 10.1210/en.2013-2176. Epub 2014 Sep 
      12.