Distinct dynorphin expression patterns with low- and high-dose estrogen treatment in the arcuate nucleus of female rats†,‡

Abstract

Kisspeptin (KISS1; encoded by Kiss1) neurons in the arcuate nucleus (ARC) coexpress tachykinin 3 (TAC3; also known as neurokinin B) and dynorphin A (PDYN). Accordingly, they are termed KNDy neurons and considered to be crucial in generating pulsatile release of gonadotropin-releasing hormone. Accumulating evidence suggests that Kiss1 and Tac3 are negatively regulated by estrogen. However, it has not been fully determined whether and how estrogen modulates Pdyn and PDYN. Here, we examined the expression of Pdyn mRNA and PDYN by in situ hybridization and immunohistochemistry, respectively, in the ARC of female rats after ovariectomy (OVX) and OVX plus low- or high-dose beta-estradiol (E2) replacement. We also investigated the effect of E2 on expression of Kiss1, KISS1, Tac3, and TAC3. Furthermore, colocalization of PDYN and estrogen receptor alpha (ESR1) was determined. Subsequently, we found that low-dose E2 treatment had no effect on Pdyn mRNA-expressing cells, but increased PDYN-immunoreactive (ir) cell numbers. In contrast, high-dose E2 treatment resulted in prominent reductions in both Pdyn mRNA-expressing and PDYN-ir cell numbers. Changes induced by low or high doses of E2 were similarly observed in the expression of Kiss1, KISS1, Tac3, and TAC3. The majority of PDYN-ir neurons coexpressed ESR1 in all groups. Our results indicate that E2 regulates the expression of PDYN, as well as KISS1 and TAC3, with regulation by E2 differing according to its levels.

Hypothalamic gene expression changes in F1 California mice (Peromyscus californicus) parents developmentally exposed to bisphenol A or ethinyl estradiol

“…In certain breast cancer cells, there is crosstalk between LEPR and ESR1 ( Fusco et al., 2010 ). In the arcuate nucleus of rats, estrogen regulates the expression of Kiss1 ( Kanaya et al., 2017 ). In the medial amygdala of mice, ESR1 but not ESR2 regulates the estrogen-induced upregulation of Kiss1 expression ( Stephens et al., 2016 ).…”

Erythropoietin-producing hepatocellular receptor A7 restrains estrogen negative feedback of luteinizing hormone via ephrin A5 in the hypothalamus of female rats

“…Four weeks after bilateral ovariectomy, 20 rats were randomly and equally divided into two groups, namely, OVX ϩ Oil and OVX ϩ E 2 groups. The OVX ϩ E2 group was treated with E2 (0.2 mg/kg body wt; Sigma Chemical Co., St. Louis, MO) daily for 7 days (1,22). E 2 was dissolved in peanut oil and administered by subcutaneous injection at 9:00 AM.…”

Does the KNDy Model for the Control of Gonadotropin-Releasing Hormone Pulses Apply to Monkeys and Humans?

“…However, this difference could reflect the absence of a progesterone peak on the day before sampling in KERKO mice (that do not have an LH surge), since progesterone secretion on proestrus in rodents is responsible for the slow pulse frequency on estrus. 34,35 Finally, there is some pharmacological evidence supporting a role for dynorphin in estrogen-negative feedback in rats, 27,36 but as noted earlier this is inconsistent with the inhibitory effects of steroids on dynorphin expression in rodents. 3 The data on steroid-negative feedback in ruminants is less extensive, but also more consistent.…”