Does Dynorphin Play a Role in the Onset of Puberty in Female Sheep?

Lopez, Justin A; Bedenbaugh, Michelle N.; McCosh, Richard B.; Weems, Peyton W.; Meadows, Lanny J.; Wisman, Brandon; Coolen, Lique M.; Goodman, Robert L.; Hileman, Stanley M.

doi:10.1111/jne.12445

Cited by 32 publications

(43 citation statements)

References 58 publications

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“…Around the time of puberty, the number of detectable PDYN neurons was lower than for KISS1 and TAC3 neurons, which is consistent with other data obtained in female sheep showing very few PDYN cells in the prepubertal ewe (Lopez et al, 2016). The striking difference in the number of neurons expressing TAC3 , KISS1 , and PDYN at this stage of development is interesting, considering that the three peptides co‐localized in the KNDy neurons in the adult sheep (Goodman et al, 2007).…”

Section: Discussionsupporting

confidence: 91%

“…The striking difference in the number of neurons expressing TAC3 , KISS1 , and PDYN at this stage of development is interesting, considering that the three peptides co‐localized in the KNDy neurons in the adult sheep (Goodman et al, 2007). This suggests that the neuroendocrine axis governing reproductive function is different in young and adult animals and, as suggested earlier (Lopez et al, 2016), a rise in progesterone levels may be necessary for induction of PDYN expression, perhaps explaining why the number of cells increased markedly in the rostral ARC, following puberty. In spite of the low number of cells, we showed that GDX reduced the number of PDYN cells.…”

Section: Discussionsupporting

confidence: 57%

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Expression of genes for Kisspeptin ( KISS1 ), Neurokinin B ( TAC3 ), Prodynorphin ( PDYN ), and gonadotropin inhibitory hormone ( RFRP ) across natural puberty in ewes

Smith

Henry

et al. 2020

Physiol Rep

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Expression of particular genes in hypothami of ewes was measured across the natural pubertal transition by in situ hybridization. The ewes were allocated to three groups (n = 4); prepubertal, postpubertal and postpubertally gonadectomized (GDX). Prepubertal sheep were euthanized at 20 weeks of age and postpubertal animals at 32 weeks. GDX sheep were also euthanized at 32 weeks, 1 week after surgery. Expression of KISS1, TAC3, PDYN in the arcuate nucleus (ARC), RFRP in the dorsomedial hypothalamus and GNRH1 in the preoptic area was quantified on a cellular basis. KISS1R expression by GNRH1 cells was quantified by double‐label in situ hybridization. Across puberty, detectable KISS1 cell number increased in the caudal ARC and whilst PDYN cell numbers were low, numbers increased in the rostral ARC. TAC3 expression did not change but RFRP expression/cell was reduced across puberty. There was no change across puberty in the number of GNRH1 cells that expressed the kisspeptin receptor (KISS1R). GDX shortly after puberty did not increase expression of any of the genes of interest. We conclude that KISS1 expression in the ARC increases during puberty in ewes and this may be a causative factor in the pubertal activation of the reproductive axis. A reduction in expression of RFRP may be a factor in the onset of puberty, removing negative tone on GNRH1 cells. The lack of changes in expression of genes following GDX suggest that the effects of gonadal hormones may differ in young and mature animals.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 57%

Expression of genes for Kisspeptin ( KISS1 ), Neurokinin B ( TAC3 ), Prodynorphin ( PDYN ), and gonadotropin inhibitory hormone ( RFRP ) across natural puberty in ewes

Smith

Henry

et al. 2020

Physiol Rep

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“…45 A similar increase in LH pulse frequency and mean levels was observed in prepubertal female sheep treated with a KOR antagonist. 49 These findings are compatible with a repressive role of Dyn on kisspeptin output from ARC Kiss1 neurons also during puberty, in line with the original KNDy hypothesis in adulthood. 39 Of note, other members of the TAC family (and possibly endogenous opioid peptides other than Dyn) are likely to participate also in the modulation of puberty onset.…”

Section: Partners Of Kisspeptins For the Control Of Puberty: Kndy Neusupporting

confidence: 81%

Neuropeptide Control of Puberty: Beyond Kisspeptins

2019

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Puberty is a fundamental developmental event in the lifespan of any individual, when sexual and somatic maturation is completed, and reproductive capacity is achieved. While the tempo of puberty is under strong genetic determination, it is also modulated by a wide array of internal and environmental cues, including, prominently, nutritional and metabolic signals. In the last decade, our understanding of the neurohormonal basis of normal puberty and its perturbations has enlarged considerably. This is illustrated by the elucidation of the essential roles of kisspeptins, encoded by the Kiss1 gene, in the hypothalamic circuits controlling puberty. Moreover, other neuropeptide pathways, convergent with kisspeptin signaling, have been pointed out as important coregulators of pubertal timing. These include the cotransmitters of Kiss1 neurons in the arcuate nucleus (ARC), neurokinin B, and dynorphin, as well as melanocortins, produced by ARC neurons expressing proopiomelanocortin, which are endowed with key roles also in the control of metabolic homeostasis. This neuropeptide setup seemingly participates, in a coordinated manner, in transmitting the regulatory actions of metabolic cues on pubertal maturation. In this function, cellular metabolic sensors, such as the AMP-activated protein kinase, and the fuel-sensing deacetylase, SIRT1, have also been shown recently to contribute to the metabolic regulation of puberty. Altogether, elucidation of the physiological roles of these signals and regulatory circuits will help uncover the intimacies of the brain control of puberty, and its alterations in conditions of metabolic stress, ranging from subnutrition to obesity.

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“…Several neural substrates such as gamma amino butyric acid, neuroestradiol and β‐endorphin (β‐ENDO) are produced by neurones in the arcuate nucleus (ARC) of the medial basal hypothalamus (MBH) and are capable of inhibiting prepubertal GnRH release. Additionally, dynorphin (DYN), another peptide produced in the ARC, has also been shown to inhibit prepubertal GnRH and thus, luteinising hormone (LH) secretion . Other investigators have shown that the administration of anti‐DYN caused increased serum LH, and that a kappa opioid receptor (KOR‐1) antagonist increased the pulsatile secretion of LH and advanced puberty .…”

Section: Introductionmentioning

confidence: 99%

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

Dees

Hiney

Srivastava

2019

J Neuroendocrinology

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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.

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Does Dynorphin Play a Role in the Onset of Puberty in Female Sheep?

Cited by 32 publications

References 58 publications

Expression of genes for Kisspeptin ( KISS1 ), Neurokinin B ( TAC3 ), Prodynorphin ( PDYN ), and gonadotropin inhibitory hormone ( RFRP ) across natural puberty in ewes

Expression of genes for Kisspeptin ( KISS1 ), Neurokinin B ( TAC3 ), Prodynorphin ( PDYN ), and gonadotropin inhibitory hormone ( RFRP ) across natural puberty in ewes

Neuropeptide Control of Puberty: Beyond Kisspeptins

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

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