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Sexually dimorphic nucleus human brain

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Science. May 31;() A sexually...

In other species, male-typical sexually dimorphic preoptic nuclei develop under the influence of gonadal testosterone exposure. Thus, we hypothesized that the oSDN develops before birth in the sheep and is organized by exposure to testosterone.

In situ hybridization for aromatase mRNA revealed a cell group in the caudal preoptic area that corresponded to the oSDN in adults. Quantitative analysis showed that the mean volume of the oSDN in late-gestation fetuses was significantly larger in male than in female lamb fetuses. We next treated a group of pregnant ewes with testosterone propionate TP from d 30—90 gestation and measured oSDN volumes in TP-exposed and control fetuses on d gestation.

The mean volume of the oSDN in female fetuses exposed to TP was significantly larger than in control females and also larger than in control and TP-exposed males. Taken together, these data demonstrate that testosterone acts during a prenatal critical period to organize the development of aromatase-expressing neurons into the male-typical oSDN in sheep. The volume of the oSDN is 2- to 3-fold greater in rams that are sexually attracted to ewes female-oriented rams than in either ewes or in rams that are sexually attracted to other rams Sexually dimorphic nucleus human brain rams.

Thus, the preference of individual rams for male vs. Earlier studies in rats clearly demonstrated that sexual partner preferences and Fos responses to pheromonal stimulation are sexually differentiated in "Sexually dimorphic nucleus human brain" to brain estrogen synthesis during early neonatal life 78.

Sexual differentiation of the sheep brain occurs before birth sometime between embryonic d 30— of a d gestation period. Systemic concentrations of T are significantly higher in male fetuses than in female fetuses during this period 14 Females born to mothers treated prenatally with T are behaviorally masculinized and defeminized.

They fail to show "Sexually dimorphic nucleus human brain" receptivity but instead display increased mounting and aggressive behavior as adults 16 — Prenatal exposure to T also blunts estrogen positive feedback on LH secretion, decreases LH sensitivity to progesterone P suppression, and advances the onset of puberty 20 To better understand the process of brain sexual differentiation in sheep, we first determined whether the oSDN was present in late-gestation fetuses d — gestation.

Once established, we then examined the effect of prenatal T exposure from d 30—90 gestation on the organization of this nucleus. Eighteen timed pregnant ewes Ovis aries of mixed Western breeds were purchased from local farmers or bred at the sheep facility at Oregon State University. Animal care was conducted in accordance with the principles and procedures outlined by the National Institutes of Health.

Accompanying Nissl-stained sections were used to confirm the presence and location of the oSDN. TP is a long-acting alkylated "Sexually dimorphic nucleus human brain" of T, which is hydrolyzed before acting Jugular blood samples were collected twice a week from the TP-treated dams throughout the treatment period and for 2 wk after treatment ended.

After about 7 wk of TP treatment, a series of frequent blood samples i. To determine what fraction of T from the maternal circulation reached the fetus, three pregnant ewes Sexually dimorphic nucleus human brain treated with TP twice weekly from d 30—85 of pregnancy as described above. This time was chosen because it approximated the elimination half-life of T in the maternal circulation.

Ewes were euthanized with an iv overdose of sodium pentobarbital Euthasol; Virbac Corp.

Blood samples were taken from the umbilical artery and vein. Heparin 10, U was given through the umbilical vein, followed by 10 ml saturated KCl to euthanize the fetus and arrest the heart in diastole. The umbilical cord was cut, and the lamb fetus was weighed. The sex of the fetus was established by direct visual inspection of the gonads. The brain was removed "Sexually dimorphic nucleus human brain" the fetal skull, and a diencephalic block that extended from the anterior margin of the optic chiasm to the mammillary bodies was dissected.

This tissue contained the major nuclei of the preoptic area, anterior hypothalamus, and medial basal hypothalamus.

This research linked an established...

Expression of cytochrome P aromatase mRNA was detected using a sheep-specific 33 P-labeled riboprobe and procedures described previously An adjacent series of brain sections were stained with thionin for anatomical verification. Two investigators unaware of the sex or age of the animals made measurements independently.

The mean of these measurements were used for statistical comparisons. T, estradiol E2and P were measured in serum aliquots from umbilical artery blood by RIA after extraction with ethyl ether and fractionation on Sephadex LH column chromatography as described previously Sexually dimorphic nucleus human brain In pregnant dams treated with TP, T was measured in maternal blood after ether extraction but without prior chromatography.

The mean percentage of recovery, water blanks, and intraassay coefficients of variation were as follows: In experiment 2, comparisons by sex and treatment group were analyzed by two-way ANOVA followed by post hoc Newman-Keuls test when appropriate.

Noncompartmental pharmacokinetic analysis of T elimination half-life was performed with Winnonlin Analysis Program version 4.

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