Solving the Puzzle: What Is the Role of Progestogens in Neovascularization?

Zhi, Xiao; Chen, Qiong

doi:10.3390/biom11111686

Cited by 4 publications

(2 citation statements)

References 166 publications

(220 reference statements)

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“…This process requires PGRMC1 [359], as well as neogenin (the second human DCC family member, also involved in netrin-mediated axon guidance) in the basal epithelial interacting with netrin [392]. Since the growth cones of vascular vessels are also directed by members of the DCC family [393,394] we could additionally hypothesize that PGRMC is directly involved in angiogenesis (for a recent review on the role of progestogens in neovascularization, see [395]), or perhaps with embryological formation of the anus. However, this is speculative and further experimental work is clearly required to establish the conserved roles of PGRMC1 tyrosines in this process, if any.…”

Section: Evolution Of Bilateria and Pgrmc1 T178 And S181mentioning

confidence: 99%

Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins

Cahill¹

2022

Front. Biosci. (Landmark Ed)

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The title usage of Unde venisti 'from where have you come' is from a now dead language (Latin) that foundationally influenced modern English (not the major influence, but an essential formative one). This is an apt analogy for how both the ancient eukaryotic and eumetazoan functions of PGRMC proteins (PGRMC1 and PGRMC2 in mammals) probably influence modern human biology: via a formative trajectory from an evolutionarily foundational fulcrum. There is an arguable probability, although not a certainty, that PGRMC-like proteins were involved in eukaryogenesis. If so, then the proto-eukaryotic ancestral protein is modelled as having initiated the oxygeninduced and CYP450 (Cytochrome P450)-mediated synthesis of sterols in the endoplasmic reticulum to regulate proto-mitochondrial activity and heme homeostasis, as well as having enabled sterol transport between endoplasmic reticulum (ER) and mitochondria membranes involving the actin cytoskeleton, transport of heme from mitochondria, and possibly the regulation/origins of mitosis/meiosis. Later, during animal evolution, the last eumetazoan common ancestor (LEUMCA) acquired PGRMC phosphorylated tyrosines coincidentally with the gastrulation organizer, Netrin/deleted in colorectal carcinoma (DCC) signaling, muscle fibers, synapsed neurons, and neural recovery via a sleep-like process. Modern PGRMC proteins regulate multiple functions, including CYP450-mediated steroidogenesis, membrane trafficking, heme homeostasis, glycolysis/Warburg effect, fatty acid metabolism, mitochondrial regulation, and genomic CpG epigenetic regulation of gene expression. The latter imposes the system of differentiation status-sensitive cell-type specific proteomic complements in multi-tissued descendants of the LEUMCA. This paper attempts to trace PGRMC functions through time, proposing that key functions were involved in early eukaryotes, and were later added upon in the LEUMCA. An accompanying paper considers the implications of this awareness for human health and disease.

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Section: Evolution Of Bilateria and Pgrmc1 T178 And S181mentioning

confidence: 99%

Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins

Cahill¹

2022

Front. Biosci. (Landmark Ed)

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“…Sex steroids, particularly PRGs, regulate neovascularization in a diverse fashion. Several studies have found a phenomenon that low concentrations of PRG potentially promote neovascularization through nPRs in a dose-dependent fashion, while high concentrations inhibit the original effect [ 150 , 151 , 152 ].…”

Section: Impacts Of Sex Steroids On Maintenance Of Vasculaturementioning

confidence: 99%

CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier

Gnanasekaran

Aickareth

Hawwar

et al. 2023

JPM

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Cerebral cavernous malformations (CCMs) arise when capillaries within the brain enlarge abnormally, causing the blood–brain barrier (BBB) to break down. The BBB serves as a sophisticated interface that controls molecular interactions between the bloodstream and the central nervous system. The neurovascular unit (NVU) is a complex structure made up of neurons, astrocytes, endothelial cells (ECs), pericytes, microglia, and basement membranes, which work together to maintain blood–brain barrier (BBB) permeability. Within the NVU, tight junctions (TJs) and adherens junctions (AJs) between endothelial cells play a critical role in regulating the permeability of the BBB. Disruptions to these junctions can compromise the BBB, potentially leading to a hemorrhagic stroke. Understanding the molecular signaling cascades that regulate BBB permeability through EC junctions is, therefore, essential. New research has demonstrated that steroids, including estrogens (ESTs), glucocorticoids (GCs), and metabolites/derivatives of progesterone (PRGs), have multifaceted effects on blood–brain barrier (BBB) permeability by regulating the expression of tight junctions (TJs) and adherens junctions (AJs). They also have anti-inflammatory effects on blood vessels. PRGs, in particular, have been found to play a significant role in maintaining BBB integrity. PRGs act through a combination of its classic and non-classic PRG receptors (nPR/mPR), which are part of a signaling network known as the CCM signaling complex (CSC). This network couples both nPR and mPR in the CmPn/CmP pathway in endothelial cells (ECs).

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Progesterone signaling in the regulation of luteal steroidogenesis

Yakın

Hela

Öktem

2023

Molecular Human Reproduction

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The corpus luteum is the major source of progesterone, the essential hormone for female reproductive function. While progesterone activity has been the subject of extensive research for decades, characterization of noncanonical progesterone receptor/signaling pathways provided a new perspective for understanding the complex signal transduction mechanisms exploited by the progesterone hormone. Deciphering these mechanisms has significant implications in the management of luteal phase disorders and early pregnancy complications. The purpose of this review is to highlight the complex mechanisms through which progesterone-induced signaling mediates luteal granulosa cell activity in the corpus luteum. Here we review the literature and discuss the up-to-date evidence on how paracrine and autocrine effects of progesterone regulate luteal steroidogenic activity. We also review the limitations of the published data and highlight future research priorities.

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Solving the Puzzle: What Is the Role of Progestogens in Neovascularization?

Cited by 4 publications

References 166 publications

Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins

Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins

CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier

Progesterone signaling in the regulation of luteal steroidogenesis

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