Phoenixin and Its Role in Reproductive Hormone Release

Clarke, Sophie; Dhillo, Waljit S.

doi:10.1055/s-0039-3400964

Cited by 9 publications

(6 citation statements)

References 34 publications

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“…Nevertheless, there is still uncertainty regarding the role of PNX in the regulation of ovarian function in mammals because most of the available evidence relates to the central regulation of the reproductive system by PNX. In addition, most of these findings are based on research conducted in a fish model [ 15 ]. Therefore, we investigated the expression and role of PNX-14 in the porcine CL.…”

Section: Discussionmentioning

confidence: 99%

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Phoenixin-14 as a novel direct regulator of porcine luteal cell functions

Mlyczyńska,

Kurowska,

Wachowska

et al. 2023

Biology of Reproduction

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Phoenixin is a neuropeptide with a well-established role in the central regulation of reproductive processes; however, knowledge regarding its role in the ovary is limited. One of the main active phoenixin isoforms is phoenixin-14, which acts through G protein–coupled receptor 173. Our research hypothesis was that phoenixin-14 is expressed in porcine corpus luteum and exerts luteotropic action by affecting the endocrine function of luteal cells through G protein–coupled receptor 173 and protein kinase signaling. Luteal cells were cultured to investigate the effect of phoenixin-14 (1–1000 nM) on endocrine function. We showed that phoenixin-14 and G protein–coupled receptor 173 are produced locally in porcine corpus luteum and their levels change during the estrous cycle. We detected phoenixin-14 immunostaining in the cytoplasm and G protein–coupled receptor 173 in the cell membrane. Plasma phoenixin levels were highest during the early luteal phase. Interestingly, insulin, luteinizing hormone, progesterone, and prostaglandins decreased phoenixin-14 levels in luteal cells. Phoenixin-14 increased progesterone, estradiol, and prostaglandin E2 secretion, but decreased prostaglandin F2α, upregulated the expression of steroidogenic enzymes, and downregulated receptors for luteinizing hormone and prostaglandin. Also, phoenixin-14 increased the expression of G protein–coupled receptor 173 and the phosphorylation of extracellular signal-regulated kinase 1/2, protein kinase B, inhibited the phosphorylation of protein kinase A, and had mixed effect on AMP-activated protein kinase alpha and protein kinase C. G protein–coupled receptor 173 and extracellular signal-regulated kinase 1/2 mediated the effect of phoenixin-14 on endocrine function of luteal cells. Our results suggest that phoenixin is produced by porcine luteal cells and can be a new regulator of their function.

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Section: Discussionmentioning

confidence: 99%

“…The PNX is considered as a peptide that regulates the female reproductive system [ 15 ]. It is a potent stimulator of luteinizing hormone (LH) secretion from the pituitary gland of rodents and fish [ 4 , 8 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Phoenixin-14 as a novel direct regulator of porcine luteal cell functions

Mlyczyńska,

Kurowska,

Wachowska

et al. 2023

Biology of Reproduction

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“…Phoenixin acts through its receptor, G protein-coupled receptor 173 (GPR173), to activate the cAMP/PKA pathway resulting in the phosphorylation of CREB (pCREB) ( Treen et al, 2016 ). PXN potentiates GnRH-stimulated LH release and increases GnRH and KISS1 gene expression, respectively, and it also raises the expression of GnRH receptor gene ( Clarke and Dhillo, 2019 ). Alternatively, compromise of PXN in vivo using siRNA led to a reduction in GnRH receptor expression in the pituitary and the delayed appearance of oestrus ( Nguyen et al, 2019 ).…”

Section: Neuropeptides That May or May Not Act Directly On Gnrh Neuronsmentioning

confidence: 99%

The neuroendocrine pathways and mechanisms for the control of the reproduction in female pigs

et al. 2021

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Within the hypothalamic-pituitary-gonad (HPG) axis, the major hierarchical component is gonadotropin-releasing hormone (GnRH) neurons, which directly or indirectly receive regulatory inputs from a wide array of regulatory signals and pathways, involving numerous circulating hormones, neuropeptides, and neurotransmitters, and which operate as a final output for the brain control of reproduction. In recent years, there has been an increasing interest in neuropeptides that have the potential to stimulate or inhibit GnRH in the hypothalamus of pigs. Among them, Kisspeptin is a key component in the precise regulation of GnRH neuron secretion activity. Besides, other neuropeptides, including neurokinin B (NKB), neuromedin B (NMB), neuromedin S (NMS), α-melanocyte-stimulating hormone (α-MSH), Phoenixin (PNX), show potential for having a stimulating effect on GnRH neurons. On the contrary, RFamide-related peptide-3 (RFRP-3), endogenous opioid peptides (EOP), neuropeptide Y (NPY), and Galanin (GAL) may play an inhibitory role in the regulation of porcine reproductive nerves and may directly or indirectly regulate GnRH neurons. By combining data from suitable model species and pigs, we aim to provide a comprehensive summary of our current understanding of the neuropeptides acting on GnRH neurons, with a particular focus on their central regulatory pathways and underlying molecular basis.

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“…Pharmacological experiments with the mature PNX peptides suggest that PNX-14 and PNX-20 act as pleiotropic neuropeptides in mammals. PNX peptides modulate heart function, memory, anxiety, food intake, and reproduction ( Clarke and Dhillo 2019 ; Schalla and Stengel 2019 ; Billert et al 2020 ; Haddock et al 2020 ; Ma et al 2020 ; Schalla et al 2020 ; Friedrich and Stengel 2021 ; Yao et al 2021 ). Strikingly for a proneuropeptide, the SMIM20 (also called MITRAC7) precursor also localizes to mitochondria in U2OS and HEK293 cells and functions as a mitochondrial chaperone during cytochrome-c oxidase complex assembly ( Dennerlein et al 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Premetazoan Origin of Neuropeptide Signaling

Yáñez-Guerra

Thiel

Jékely

2022

Molecular Biology and Evolution

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Neuropeptides are a diverse class of signalling molecules in metazoans. They occur in all animals with a nervous system and also in neuron-less placozoans. However, their origin has remained unclear because no neuropeptide shows deep homology across lineages and none have been found in sponges. Here, we identify two neuropeptide precursors, phoenixin and nesfatin, with broad evolutionary conservation. By database searches, sequence alignments and gene-structure comparisons we show that both precursors are present in bilaterians, cnidarians, ctenophores and sponges. We also found phoenixin and a secreted nesfatin precursor homolog in the choanoflagellate Salpingoeca rosetta. Phoenixin in particular, is highly conserved, including its cleavage sites, suggesting that prohormone processing occurs also in choanoflagellates. In addition, based on phyletic patterns and negative pharmacological assays we question the originally proposed GPR-173 (SREB3) as a phoenixin receptor. Our findings revealed that secreted neuropeptide homologs derived from longer precursors have pre-metazoan origins and thus evolved before neurons.

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Phoenixin and Its Role in Reproductive Hormone Release

Cited by 9 publications

References 34 publications

Phoenixin-14 as a novel direct regulator of porcine luteal cell functions

Phoenixin-14 as a novel direct regulator of porcine luteal cell functions

The neuroendocrine pathways and mechanisms for the control of the reproduction in female pigs

Premetazoan Origin of Neuropeptide Signaling

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