Regulation of progesterone receptor expression by estradiol is dependent on age, sex and region in the rat brain

Abstract

Progesterone receptor (PR) expression is highly dependent on estradiol in the medial preoptic nucleus (MPN) and the ventromedial nucleus (VMN) of the adult rat brain. During development, males express high levels of PR in the MPN, whereas females have virtually no PR, a sex difference resulting entirely from differential exposure to estradiol. Because PR is also estradiol dependent in the adult VMN, the present study examined the regulation of PR immunoreactivity (PRir) in the developing VMN. Surprisingly, PRir was present at high levels in the VMN of both neonatal males and females. In the neonatal VMN, PR expression was dependent on gonadal hormones in males but not females. When females were ovariectomized and exposed to estradiol at various ages from neonatal to adulthood, estradiol reliably induced PRir in the MPN at postnatal d 7 but failed to induce PRir in the VMN of the same animals. Only later in development, around postnatal d 14, did estradiol increase PRir in the female VMN. There appears to be a developmental switch in the VMN when PR expression changes from estradiol independent to estradiol dependent. Furthermore, this switch is anatomically specific and does not exist in the MPN. The present results indicate that the regulation of PR expression by estradiol is dependent on age, sex, and brain region, suggesting that PR may play a critical but specific role in the normal development of these reproductively important brain areas. In addition, the neonatal female VMN may provide a unique model in which to examine the mechanisms underlying the specificity of steroid-induced gene expression.

Figure 1

PRir in the VMN of P7 and P14 is sexually dimorphic. A, The relative amount of PRir in males (black bars) and females (white bars). PRir in representative sections of P7 male (B) and female (C). *, Significantly different from the opposite sex of the same age. Bar, 100 μm.

Figure 2

PRir in the MPN of P7 and P14 is sexually dimorphic. A, The relative amount of PRir in males (black bars) and females (white bars). PRir in representative sections of P7 male (B) and female (C). *, Significantly different from the opposite sex of the same age. Bar, 100 μm.

Figure 3

PRir in the VMN in P4 males (A and B) that were sham castrated (A) or castrated (B) on the day of birth or in P4 females (C and D) that were sham ovariectomized (C) or ovariectomized (D) on the day of birth. Bar, 100 μm.

Figure 4

Hormonal regulation of PRir on P4. The relative amount of PRir in the VMN (A) or the MPN (B) in P4 males and females that were either GDX (white bars) or sham-GDX (Sham; black bars) on the day of birth. *, Significantly different from sham.

Figure 5

PRir in the VMN in P14 males (A and B) that were sham-castrated (A) or castrated (B) on the day of birth or in P14 females (C and D) that were sham-ovariectomized (C) or ovariectomized (D) on the day of birth. Bar, 100 μm.

Figure 6

Hormonal regulation of PRir on P14. The relative amount of PRir in the VMN (A) or the MPN (B) in P14 males and females that were either GDX (white bars) or sham-gonadectomized (Sham; black bars) on the day of birth. *, Significantly different from sham.

Figure 7

Estradiol regulation of PRir is developmentally dependent in the VMN. A, The relative amount of PRir in the VMN of females that were ovariectomized 7 d before the animals were killed and administered either oil (black bars) or EB (white bars) 48 h before the animals were killed. PRir in representative sections of P7 ovariectomized females that were treated with EB (B) or the oil vehicle alone (C). n.s., Not significant. *, Significantly different from oil-treated controls. Bar, 100 μm.

Figure 8

Estradiol consistently regulated PRir in the MPN of females at all ages. A, The relative amount of PRir in the MPN of females that were ovariectomized 7 d before the animals were killed and administered either oil (black bars) or EB (white bars) 48 h before the animals were killed. PRir in representative sections of P7 ovariectomized females that were treated with EB (B) or the oil vehicle alone (C). n.s., Not significant. *, Significantly different from oil-treated controls.

Figure 9

Alterations in uterine weights after exposure to oil vehicle (oil) or EB. Mean (±sem) uterine weight (milligrams) in ovariectomized females at P7, P14, P35, P49, and P67 that were treated 48 h prior with either EB (white bars) or oil (black bars). *, Significantly different from oil-treated controls. Numbers in parentheses indicate the percent increase in mean uterine weight in EB-treated females, compared with oil-treated controls.