Regulation of neuronal oxytocin mRNA by ovarian steroids in the mature and developing hypothalamus.

Abstract

We have examined the changes in neuronal expression of oxytocin mRNA in the perinatal and mature female rat as a function of endogenous gonadal steroids. Northern blot analysis demonstrated a significant developmental increase in the abundance of oxytocin mRNA in the female brain concomitant with puberty. Ovariectomy of adult females decreased total brain oxytocin mRNA to significantly lower levels. In contrast, lactating mothers had increased levels of neuronal oxytocin mRNA. In situ hybridization analysis of neuronal oxytocin mRNA in adolescent, mature virgin, and ovariectomized virgin female brains demonstrated that the location and number of neurons expressing oxytocin mRNA was unchanged and that total brain oxytocin mRNA differences were attributable to amounts expressed per neuron. Differences in mRNA abundance were noted in oxytocin neurons throughout the hypothalamus, including those known to project as magnocellular neurons to the neurohypophysis and those of parvocellular origin thought to make wholly intracerebral connections. This developmental and dynamic regulation of oxytocin mRNA levels during gonadal maturation may coordinate the peripheral and central effects of this peptide on the reproductive biology of the female rat.The nonapeptide oxytocin has been implicated as a neurosecretory peptide involved in labor and milk ejection and as a centrally active neuropeptide responsible for stimulating sexual and maternal behaviors (1-4). Oxytocinergic neurons in the supraoptic and paraventricular nuclei of the hypothalamus project to the posterior pituitary where the peptide is released into the circulation (5). In addition, oxytocinergic parvocellular neurons have been shown to project to many extrahypothalamic brain areas, including regions of spinal cord, brainstem, and forebrain (5, 6).Ovarian steroids, which play a central role in the control of reproductive function, influence both neurosecretory and intracerebrally projecting oxytocinergic neurons. Estrogen treatment stimulates the release of oxytocin into the peripheral circulation (7), induces oxytocin binding sites in the brain (8), influences the electrical activity ofoxytocinergic neurons (9), and alters the pattern of oxytocinergic cells and fibers in the brain, as detected by immunocytochemistry (10-12). How estrogen mediates these changes is unknown, although a subpopulation of oxytocinergic neurons have binding sites for estradiol (13,14).We are interested in neural correlates of behavioral changes that accompany puberty. To determine whether the oxytocinergic system is modified by increased ovarian steroids during female adolescence, we have investigated neuronal levels of oxytocin mRNA before, during, and after puberty using Northern blot and in situ hybridization analyses. These studies demonstrate that there is a coordinate increase in the abundance of oxytocin mRNA in both neurosecretory and centrally projecting neurons concomitant with puberty. Ovariectomy of mature females leads to a decrease in the levels of oxytocin mRNA...

Effect of the interaction between food state and the action of estrogen on oxytocinergic system activity

“…Taken together, these studies indicate that the action of estrogen on magnocellular neurones contributes to the regulation of OT release , Van Tol et al 1988, Miller et al 1989, Amico et al 1995, Salonia et al 2005, Somponpun 2007). In contrast, some studies have found that estrogen has no significant effect on OT expression in the PVN (Van Tol et al 1988, Crowley et al 1993, while yet another group has shown that treatment with estrogen decreases the expression of OT mRNA in the PVN of ovariectomized rats (OVX; Shughrue et al 2002).…”

“…Some studies have shown a variation both in the levels of OT in the PVN, the SON and the neurohypophysis and in the plasma concentration of OT during the estrous cycle, with higher oxytocinergic activity during pro-estrous (Crowley et al 1978, Sarkar & Gibbs 1984, Greer et al 1986, Windle & Forsling 1993. The expression of OT mRNA in the magnocellular neurones of the PVN (Van Tol et al 1988) increases at the onset of puberty and decreases after castration (Miller et al 1989), suggesting a possible influence of estrogen on OT expression levels.…”

Effects of Estradiol-17.BETA. on Oxytocin and Progesterone Release of the Bovine Corpus Luteum during the Estrous Cycle.

“…E 2 (1 nmol/l; Fig. 3B) induced a significant inhibition during infusion on days <5, days 8-12 and days [15][16][17][18]. E 2 at a lower dose (10 pmol/l; Fig.…”

“…P 4 values (nmol/l) varied (P>0.05) with the luteal phase from 11.15 ± 1.65 for days 8-12 to 7.0 ± 0.63 for days [15][16][17][18] (Fig. 1A), whereas Fig.…”

Cell‐Specific Expression of the Rat Oxytocin Gene in Transgenic Mice

“…Similar elements in rat and human OT 5'-flanking regions have also been described by Burbach et al (5). The latter authors detected no estrogen receptors or changes in OT mRNA levels there following ovariectomy and replacement with estradiol, although Miller et al (6) described lower levels in ovariectomized or prepubescent female rats. In addition, OT neurons concentrate estradiol (7).…”