Expression of Ovarian Steroid Hormone Receptors in Tuberoinfundibular Dopaminergic Neurones During Pregnancy and Lactation

Abstract

During late-pregnancy, tuberoinfundibular dopaminergic (TIDA) neurones, a critical component of the negative-feedback loop regulating prolactin secretion, become unresponsive to the stimulatory effects of prolactin. The change in TIDA responsiveness to prolactin at this time results in a decrease in dopamine secretion and a prolactin surge. As the onset of parturition and the antepartum prolactin surge depend on the withdrawal of progesterone in the presence of oestrogen, it is likely that ovarian steroid hormones mediate this change in TIDA responsiveness. To determine whether ovarian steroids can directly modulate TIDA activity, and whether changes of receptor numbers might contribute to overall steroid-regulation of these neurones, we investigated the level of oestrogen receptor alpha (ERalpha) and progesterone receptor (PR) expression within TIDA neurones during pregnancy and lactation. Animals were sacrificed on dioestrous, days 12, 19 and 21 of pregnancy and day 5 of lactation, and the proportion of TIDA neurones expressing ERalpha or PR, as well as the total number of PR expressing cells within the arcuate nucleus, was determined. Approximately 75% and 55% of tyrosine hydroxylase neurones expressed ERalpha and PR, respectively. Levels of steroid receptor expression within TIDA neurones remained fairly constant, except for an increase in ERalpha on days 12 and 19 of pregnancy compared to dioestrous and lactation day 5. The presence of steroid receptors on TIDA neurones during pregnancy and lactation supports the concept of a direct effect of steroid hormones on these neurones at this time. Thus, steroid hormones may directly act on TIDA neurones to regulate maternal prolactin secretion. The relatively stable level of expression during late pregnancy suggests that a shift in steroid receptor expression during late pregnancy does not contribute to the change in TIDA responsiveness to prolactin at this time.

Hypothalamic Effects of Tamoxifen on Oestrogen Regulation of Luteinising Hormone and Prolactin Secretion in Female Rats

“…This reinforces the efficacy of S 40 pTH staining in reflecting TH activity in nerve terminals of TIDA neurones and is in line with the results of a previous study reporting TH and S 40 pTH labelling in the ME of lactating mice . The TIDA neurones express ERα and there is practically no expression of ERß in the ARC . Thus, taken together with these previous reports, our findings suggest that ERα activation is required for E 2 ‐induced down regulation of TH activity in the ME to generate the PRL surge.…”

The anti-androgen combination, flutamide plus finasteride, paradoxically suppressed LH and androgen concentrations in pregnant spotted hyenas, but not in males

“…Modulation of hormone negative feedback during pregnancy is not uncommon, and in other species it has been reported for prolactin [25] and the hypothalamic-pituitary-adrenal (HPA) axis [6, 12]. Therefore, the negative feedback qualities of the LH - androgen system may be altered during pregnancy in the spotted hyena, which may have led to the unexpected responses to F&F. The placenta contributes to the modulation of the HPA axis in other species [28], and the placenta is a significant source of testosterone in the spotted hyena [16, 29].…”

Chronic estradiol exposure induces oxidative stress in the hypothalamus to decrease hypothalamic dopamine and cause hyperprolactinemia

“…The tuberoinfundibular dopaminergic (TIDA) system is one of the most estrogen-sensitive neuronal systems in the hypothalamus (37), and estrogen's effects are known to be mediated through estrogen receptor-␣ (ER-␣) (41). The cell bodies of TIDA neurons are located in the arcuate nucleus (AN), and their terminals reach the median eminence (ME).…”