Regulation of prepubertal dynorphin secretion in the medial basal hypothalamus of the female rat

Abstract

The onset of puberty is the result of an increase in secretion of hypothalamic gonadotrophin‐releasing hormone (GnRH). This action is a result of not only the development of stimulatory inputs to its release, but also the gradual decrease in inhibitory inputs that restrain release of the peptide prior to pubertal onset. Dynorphin (DYN) is one of the inhibitory inputs produced in the medial basal hypothalamus (MBH); however, little is known about what substance(s) control its prepubertal synthesis and release. Because neurokinin B (NKB) increases in the hypothalamus as puberty approaches, we considered it a candidate for such a role. An initial study investigated the acute effects of an NKB agonist, senktide, on the secretion of DYN from MBH tissues incubated in vitro. In other experiments, central injections of senktide were administered to animals for 4 days then MBHs were collected for assessment of DYN synthesis or for the in vitro secretion of both DYN and GnRH. Because insulin‐like growth factor (IGF)‐1 has been shown to play an important role at puberty, additional animals received central injections of this peptide for 4 days to assess NKB and DYN synthesis or the in vitro secretion of NKB. The results obtained show that senktide administration up‐regulates the NKB receptor protein, at the same time as suppressing the DYN and its receptor. Senktide consistently suppressed DYN and elevated GnRH secretion in the same tissue incubates from both the acute and chronic studies. IGF‐1 administration caused an increase in NKB protein, at the same time as decreasing DYN protein. Furthermore, the central administration of IGF‐1 caused an increase in NKB release, an action blocked by the IGF‐1 receptor blocker, JB‐1. These results indicate that the IGF‐1/NKB pathway contributes to suppressing the DYN inhibitory tone on prepubertal GnRH secretion and thus facilitates the puberty‐related increase in the release of GnRH to accelerate the onset of puberty.

IGF-1 Influences Gonadotropin-Releasing Hormone Regulation of Puberty

“…While the above in vitro study suggested that NKB inhibits DYN secretion, animal studies were needed to discern a better understanding of this action within the MBH. In this regard, that same study [87] showed an increase in protein expression of the NK3R (Fig. 3a), along with suppressed protein expressions of DYN (Fig.…”

“…Therefore, it was important to determine whether the tachykinin, NKB, which increases in the MBH as puberty approaches [86], would cause the suppression of prepubertal DYN release and thus facilitate the pubertyrelated rise in GnRH/LH secretion [20,82]. An initial study [87] assessed MBH explants from late juvenile female rats exposed to senktide, an NK3R agonist, and revealed a dose-dependent inhibition of DYN release, which coincided with an increase in GnRH release from the same tissue block. That same study also showed that both actions of senktide were blocked by the prior central administration of an antagonist to NK3R.…”

“…This antagonist has been shown to delay the onset of puberty in female rats [88] and to block the NKB stimulation of LH release [20,82,83]. Importantly, the release of β-endorphin, another opioid inhibitor of GnRH secretion [63] produced in the ARC, was unaffected by senktide [87].…”

Adolescent intermittent ethanol exposure effects on kappa opioid receptor mediated dopamine transmission: Sex and age of exposure matter

“…While prenatal ethanol exposure did not result in sex differences [56,57], it is possible that ethanol exposure during the peri-pubertal period may affect the dynorphin/KOR system in adulthood. Secretion of dynorphin in the hypothalamus reduces at the onset of puberty in female rats [61]. Alcohol exposure between PD 27 and 33 in female rats, however, resulted in elevated synthesis of dynorphin in this region [62].…”

Adolescent Intermittent Ethanol Exposure Effects on Kappa Opioid Receptor Mediated Dopamine Transmission: Sex and Age of Exposure Matter

“…While prenatal ethanol exposure did not result in sex differences [ 60 , 61 ], it is possible that ethanol exposure during the peri-pubertal period may affect the dynorphin/KOR system in adulthood. Secretion of dynorphin in the hypothalamus decreases at the onset of puberty in female rats [ 65 ]. Alcohol exposure between PD 27 and 33 in female rats, however, results in elevated synthesis of dynorphin in this region [ 66 ].…”