Influence of dynorphin on estradiol- and cervical stimulation-induced prolactin surges in ovariectomized rats

Abstract

Prolactin is an anterior pituitary hormone necessary for fertility, pregnancy maintenance, lactation, and aspects of maternal behavior. In rodents, there is a surge of prolactin on the afternoon of proestrus, and a semi-circadian pattern of prolactin surges during early pregnancy, with a diurnal and nocturnal surge every day. Both of these patterns can be replicated in ovariectomized rats. A prior study demonstrated that central antagonism of κ-opioid receptors, the target of dynorphin, largely abolished the nocturnal prolactin surge in pregnant rats. We build on this to determine whether dynorphin, perhaps from the arcuate population that co-express kisspeptin, neurokinin B, and dynorphin (KNDy neurons), also contributes to the estradiol- or cervical stimulation-induced surges in ovariectomized rats. Ovariectomized rats were treated with either estradiol or cervical stimulation to induce prolactin surge(s). Blood samples were taken around the expected surge time to determine the effect of either acute κ-opioid receptor antagonism or previous chemical ablation of the KNDy population on prolactin levels. Dynorphin antagonism does significantly disrupt the nocturnal prolactin surge, but it does not contribute to the estradiol-induced surge. Chemical ablation of KNDy neurons had opposite effects; ablation of 40 % of the KNDy neurons had no impact on the nocturnal prolactin surge, while a somewhat larger ablation significantly reduced the size of the estradiol-induced surge. We conclude that dynorphin is likely a controlling factor for the nocturnal surge induced by cervical stimulation, and that other KNDy neuron products must play a role in the estradiol-induced surge.

Kisspeptin/Neurokinin B/Dynorphin (KNDy) cells as integrators of diverse internal and external cues: evidence from viral-based monosynaptic tract-tracing in mice

“…Consistent with this hypothesis, KNDy neurons have been implicated in a number of reproductive and non-reproductive process. This includes steroid hormone feedback control of gonadotropin secretion 10 , the effects of metabolic 11,12 and stress-induced cues 13,14 on reproduction, seasonal breeding 15–18 , puberty 19–21 and the influence of gonadal steroids on prolactin 22 and thermoregulation 23–25 . However, the mechanisms through which KNDy neurons regulate these processes are unclear.…”

Partial loss of arcuate kisspeptin neurons in female rats stimulates luteinizing hormone and decreases prolactin secretion induced by estradiol

“…Previous studies using intra-ARC NK3-SAP in rats have reported that KNDy neuron ablation of variable degrees results in increased E 2induced LH surge 23,24 and attenuated PRL surge. 25 Here, the partial lesion of KNDy neurons caused irregular estrous cyclicity but no impairment of ovulation. To further investigate their capacity to generate LH and PRL surges, rats were subsequently OVX and treated with a positive-feedback dose of E 2 for the concurrent evaluation of LH and PRL secretion, measured in serial tail-tip blood samples (Figure 4).…”

“…This experiment aimed to evaluate the effects of the neurochemical lesion of KNDy neurons on the E 2 regulation of gonadal and PRL axes in female rats. By contrast to previous studies investigating NK3-SAP ablation of KNDy neurons, [22][23][24][25] we used a method of tailtip blood collection coupled with an enzyme-linked immunosorbent assay (ELISA) to LH and PRL that requires a low blood volume in each bleeding session and allows for serial blood sampling over time without the interfering effects of anesthesia or surgeries of bloodvein cannulation. Moreover, we employed a longitudinal approach in which the same rats were evaluated for all the parameters tested (Figure 1A).…”

“…24 Additionally, the moderate lesion of KNDy neurons has been found to attenuate the magnitude of the E 2 -induced PRL surge, although the neuroendocrine pathway involved was not determined. 25 Thus, there is sparse information on the distinct roles of KNDy neurons in the gonadal and PRL axes, whereas their physiological relevance in conveying the different effects of E 2 to LH and PRL remains unclear.…”

Analgesic effect of flurbiprofen ester and its effect on serum inflammatory factors and Β-endorphin expression in rats with incision pain

“…The analgesic effect of endorphin is strong, and it enhances the release of hormones such as auxin, prolactin, somatostatin and glucagon [6]. Surgical wounds cause tissue injury, release of inflammatory factors, inflammatory reactions and hyperalgesia [7].…”