Reduced gonadotroph stimulation by ethanolamine plasmalogens in old bovine brains

Abstract

Ethanolamine plasmalogens (EPls), unique alkenylacyl-glycerophospholipids, are the only known ligands of G-protein-coupled receptor 61—a novel receptor co-localised with gonadotropin-releasing hormone receptors on anterior pituitary gonadotrophs. Brain EPl decreases with age. Commercial EPl—extracted from the cattle brain (unidentified age)—can independently stimulate FSH secretion from gonadotrophs. We hypothesised that there exists an age-related difference in the quality, quantity, and ability of bovine brain EPls to stimulate bovine gonadotrophs. We compared the brains of young (about 26 month old heifers) and old (about 90 month old cows) Japanese Black bovines, including EPls obtained from both groups. Additionally, mRNA expressions of the EPl biosynthesis enzymes, glyceronephosphate O-acyltransferase, alkylglycerone phosphate synthase, and fatty acyl-CoA reductase 1 (FAR1) were evaluated in young and old hypothalami. The old-brain EPl did not stimulate FSH secretion from gonadotrophs, unlike the young-brain EPl. Molecular species of EPl were compared using two-dimensional liquid chromatography-mass spectrometry. We identified 20 EPl molecular species of which three and three exhibited lower (P < 0.05) and higher (P < 0.05) ratios, respectively, in old compared to young brains. In addition, quantitative reverse transcription-polymerase chain reaction detected higher FAR1 levels in the POA, but not in the ARC&ME tissues, of old cows than that of fertile young heifers. Therefore, old-brain EPl may be associated with age-related infertility.

Ethanolamine plasmalogens derived from whale brain stimulate both follicle‐stimulating hormone and luteinizing hormone secretion by bovine gonadotrophs

“…Another important reason is that important synthesis enzymes, such as GNPAT, AGPS, and FAR1, are expressed in the preoptic area, arcuate nucleus, and median eminence including the secretory zone (Kadokawa et al, 2021;Figure S1). Whale brain EPls stimulated LH and FSH secretion from bovine AP cells.…”

“…We used cultured bovine AP cell models as described in previous studies to evaluate the effects of various hormones, including insulinlike growth factor I, kisspeptin, estrogens, anti-Müllerian hormone, and EPl (Ezzat et al, 2010;Hashizume et al, 2002;Kadokawa et al, 2021Kereilwe, Pandey, Borromeo, & Kadokawa, 2018;Otsuka & Kadokawa, 2017).…”

“…This system consisted of (1) normal-phase HPLC to separate targeted phospholipids (phosphatidylethanolamines, in this study) from other lipid classes in the first column (firstdimensional HPLC separation); (2) a switching valve, trapping column, and make-up pump to trap the target lipid class; (3) reverse-phase HPLC to separate the target lipid classes in the second column (second-dimensional HPLC separation); and (4) a charged aerosol detector and electrospray ionization-mass spectrometer to identify and quantify EPl molecular species. The components of the 2D LC-MS system, such as columns, pumps, autosampler, detectors, electrospray ionization-mass spectrometer, and software, were the same as those previously reported (Kadokawa et al, 2021;Takahashi et al, 2018). In order to estimate the EPl purity, defined as the ratio of the peak area of EPl to the peak area of phosphatidylethanolamine, phosphatidylethanolamine concentrations of lipid samples that underwent only phospholipase A 1 hydrolysis were compared with those of the samples that underwent both phospholipase A 1 and HCl hydrolysis .…”

Spike protein of SARS-CoV-2 suppresses gonadotrophin secretion from bovine anterior pituitaries

“…Unlike human AP glands, bovine AP glands can be obtained for primary culture as they can be collected from slaughterhouses. Indeed, using bovine gonadotrophs, we discovered new receptors that control LH and FSH secretion, colocalizing with gonadotropin-releasing hormone (GnRH) receptor (GnRHR) in the lipid rafts of bovine gonadotrophs [ 7 , 11 , 12 , 13 ]. Bovine ACE2 contains most of the key residues for the receptor-binding domain of SARS-CoV-2 [ 14 ] (details are shown in Supplementary Fig.1 ), and SARS-CoV-2 replicates in bovine respiratory tissues [ 15 ].…”

Plasmalogen-Mediated Activation of GPCR21 Regulates Cytolytic Activity of NK Cells against the Target Cells

“…In addition, we have also found that Pls have neuroprotective effects and can induce cellular signaling such as ERK and Akt via the G proteincoupled receptors (GPCRs), including GPCR21 (912). Growing evidence suggests that these special lipids could function as ligands that activate the GPCRs to elicit a biological function (13,14). Therefore, if NK cells express these GPCRs, it could be possible that Pls might activate these GPCRs to regulate NK cell functions.…”