Multifunctional Hormone Research Articles

Melatonin: What Do We Know so Far about the Activity of This Hormone against COVID-19?

Melatonin is a multifunctional hormone that has emerged as an important active or adjuvant drug to be used at different COVID-19 therapy stages. Its antiviral activity has been quite substantiated by several reports and analyzed in clinical trials; the ones in progress will be herein addressed. Neuroprotection is an important topic when it comes to melatonin’s action on SARS-CoV-2. The perspective and future of melatonin’s action on COVID-19 will be also addressed in the current study.

Adropin Stimulates Proliferation and Inhibits Adrenocortical Steroidogenesis in the Human Adrenal Carcinoma (HAC15) Cell Line.

Adropin is a multifunctional peptide hormone encoded by the ENHO (energy homeostasis associated) gene. It plays a role in mechanisms related to increased adiposity, insulin resistance, as well as glucose, and lipid metabolism. The low adropin levels are strongly associated with obesity independent insulin resistance. On the other hand, overexpression or exogenous administration of adropin improves glucose homeostasis. The multidirectional, adropin-related effects associated with the regulation of metabolism in humans also appear to be attributable to the effects of this peptide on the activity of various elements of the endocrine system including adrenal cortex. Therefore, the main purpose of the present study was to investigate the effect of adropin on proliferation and secretory activity in the human HAC15 adrenal carcinoma cell line. In this study, we obtained several highly interesting findings. First, GPR19, the main candidate sensitizer of adrenocortical cells to adropin, was expressed in HAC15 cells. Moreover, GPR19 expression was relatively stable and not regulated by ACTH, forskolin, or adropin itself. Our findings also suggest that adropin has the capacity to decrease expression levels of steroidogenic genes such as steroidogenic acute regulatory protein (StAR) and CYP11A1, which then led to a statistically significant inhibition in cortisol and aldosterone biosynthesis and secretion. Based on whole transcriptome study and research involving transforming growth factor (TGF)-β type I receptor kinase inhibitor we demonstrated that attenuation of steroidogenesis caused by adropin is mediated by the TGF-β signaling pathway likely to act through transactivation mechanism. We found that HAC15 cells treated with adropin presented significantly higher proliferation levels than untreated cells. Using specific intracellular inhibitors, we showed that adropin stimulate proliferation via ERK1/2 and AKT dependent signaling pathways. We have also demonstrated that expression of GPR19 is elevated in adrenocortical carcinoma in relation to normal adrenal glands. High level of GPR19 expression in adrenocortical carcinoma may constitute a negative prognostic factor of disease progression.

Cell-surface receptors enable perception of extracellular cytokinins

Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience. Although their Histidine Kinase receptors are substantially localised to the endoplasmic reticulum, cellular sites of cytokinin perception and importance of spatially heterogeneous cytokinin distribution continue to be debated. Here we show that cytokinin perception by plasma membrane receptors is an effective additional path for cytokinin response. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP) closely matches intracellular cytokinin content in roots, yet we also find cytokinins in extracellular fluid, potentially enabling action at the cell surface. Cytokinins covalently linked to beads that could not pass the plasma membrane increased expression of both TCSn::GFP and Cytokinin Response Factors. Super-resolution microscopy of GFP-labelled receptors and diminished TCSn::GFP response to immobilised cytokinins in cytokinin receptor mutants, further indicate that receptors can function at the cell surface. We argue that dual intracellular and surface locations may augment flexibility of cytokinin responses.

Intrinsic disorder perspective of an interplay between the renin-angiotensin-aldosterone system and SARS-CoV-2.

The novel severe acute respiratory syndrome (SARS) coronavirus SARS-CoV-2 walks the planet causing the rapid spread of the CoV disease 2019 (COVID-19) that has especially deleterious consequences for the patients with underlying cardiovascular diseases (CVDs). Entry of the SARS-CoV-2 into the host cell involves interaction of the virus (via the receptor-binding domain (RBD) of its spike glycoprotein) with the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) followed by the virus-ACE2 complex internalization by the cell. Since ACE2 is expressed in various tissues, such as brain, gut, heart, kidney, and lung, and since these organs represent obvious targets for the SARS-CoV-2 infection, therapeutic approaches were developed to either inhibit ACE2 or reduce its expression as a means of prevention of the virus entry into the corresponding host cells. The problem here is that in addition to be a receptor for the SARS-CoV-2 entry into the host cells, ACE2 acts as a key component of the renin-angiotensin-aldosterone system (RAAS) aimed at the generation of a cascade of vasoactive peptides coordinating several physiological processes. In RAAS, ACE2 degrades angiotensin II, which is a multifunctional CVD-promoting peptide hormone and converts it to a heptapeptide angiotensin-(1–7) acting as the angiotensin II antagonist. As protein multifunctionality is commonly associated with the presence of flexible or disordered regions, we analyze here the intrinsic disorder predisposition of major players related to the SARS-CoV-2 – RAAS axis. We show that all considered proteins contain intrinsically disordered regions that might have specific functions. Since intrinsic disorder might play a role in the functionality of query proteins and be related to the COVID-19 pathogenesis, this work represents an important disorder-based outlook of an interplay between the renin-angiotensin-aldosterone system and SARS-CoV-2. It also suggests that consideration of the intrinsic disorder phenomenon should be added to the modern arsenal of means for drug development.

Insights into exogenous melatonin associated with phenylalanine metabolism in postharvest strawberry

Melatonin is a kind of multifunctional hormone, analogous to indoleacetic acid in structure. To uncover the relationship between exogenous melatonin and the phenylalanine pathway, the liquid chromatography mass spectrometry (LCMS) was performed to quantify endogenous melatonin and individual anthocyanin content. RT-qPCR was used to explore the expression of primary genes involved in anthocyanin biosynthesis. In the present study, we found that the morphology and endogenous melatonin content of strawberries showed a significant improvement and increase in the M50 compared with the other groups. Additionally, anthocyanin accumulation and genes up-regulation, in both the M50 and the M100, all revealed higher levels than that of the control. In conclusion, this work revealed the positive relationship between exogenous melatonin and the phenylalanine metabolism of strawberries.

Toward the Understanding of Small Protein-Mediated Collagen Intrafibrillar Mineralization.

The design of improved materials for orthopedic implants and bone tissue engineering scaffolds relies on materials mimicking the properties of bone. Calcium phosphate (Ca-PO4)-mineralized collagen fibrils arranged in a characteristic hierarchical structure constitute the building blocks of mineralized vertebrate tissues and control their biomechanical and biochemical properties. Large, flexible, acidic noncollagenous proteins (ANCPs) have been shown to influence collagen mineralization but little is known about mineralization mechanisms with the aid of small proteins. Osteocalcin (OCN) is a small, highly structured biomolecule known as a multifunctional hormone in its undercarboxylated form. Here, we examined the potential mechanism of collagen intrafibrillar mineralization in vitro mediated by OCN as a model protein. Rapid and random extrafibrillar mineralization of flakey Ca-PO4 particles was observed by transmission electron microscopy mainly on the outer surfaces of collagen fibrils of a preformed collagen scaffold in the absence of the protein. In contrast, the protein stabilized hydrated, spherical nanoclusters of Ca-PO4 on the outer surface of the fibrils, thereby retarding extrafibrillar mineralization. The nanoclusters then infiltrated the fibrils resulting in intrafibrillar mineralization with HAP crystals aligned with the fibrils. This mechanism is similar to that observed for unstructured ANCPs. Results of fibrillogenesis and immunogold labeling studies showed that OCN was associated primarily with the fibrils, consistent with ex vivo studies on mineralizing turkey tendon. The present findings contribute to expanding our understanding of collagen intrafibrillar mineralization and provide insight into design synthetic macromolecular matrices for orthopedic implants and bone regeneration.

Changes of circulating neuregulin 4 and its relationship with 25-hydroxy vitamin D and other diabetic vascular complications in patients with diabetic peripheral neuropathy

BackgroundNeuregulin 4 (Nrg4) is a novel neurotrophic adipokine associated with the development of diabetic peripheral neuropathy (DPN), however, the pathological mechanism remains poorly understood. The purpose of our study was to investigate the association of circulating Nrg4 with DPN and 25-hydroxy vitamin D [25(OH)D], a multifunctional secosteroid hormone that regulates other neurotrophic factors and adipokines gene expression, and other diabetic vascular complications.MethodsCirculating Nrg4 levels were measured with an ELISA kit in 164 newly diagnosed type 2 diabetes mellitus (nT2DM) patients. The relationship between circulating Nrg4 and DPN and other parameters was analyzed.ResultsCirculating Nrg4 levels were significantly lower in nT2DM patients with DPN than those without, and subjects in the highest quartile of circulating Nrg4 had significantly lower vibration perception threshold (VPT), the prevalence of DPN, the proportion of persons with VPT > 25 V, and significantly higher circulating 25(OH)D (all P < 0.01). Moreover, circulating Nrg4 was positively and independently associated with 25(OH)D, and was negatively with VPT (P < 0.01 or P < 0.05), but showed no associations with the prevalence of peripheral arterial disease, diabetic nephropathy, and diabetic retinopathy (all P > 0.05). Additionally,the prevalence of DPN and risk of DPN development were progressively decreased with increasing circulating Nrg4 quartiles, independently of potential confounding factors.ConclusionsThese data demonstrate that decreased levels of circulating Nrg4 might lead to the development of DPN through its close interaction with circulating 25(OH)D not with other diabetic vascular complications. Further prospective studies are needed to identify our findings in these populations.

Role of Serum Leptin in the Diagnosis and Prognosis of Hepatocellular Carcinoma in Egyptian Cirrhotic Patients

Abstract Background: Hepatocellular carcinoma is the most com-mon primary hepatic malignancy with an average survival rate of 6-20 months. The primary etiology of hepatocellular carcinoma in Egyptian patients is liver cirrhosis. Alfa fetopro-tein is the most commonly used biomarker for HCC diagnosis, in spite of its low sensitivity and specificity in HCC screening; it is usually combined with ultrasound for early detection of HCC. Leptin is a multifunctional peptide hormone that is produced by adipocytes with neuroendocrine activity. Leptin is postulated to increase the hepatic response to different stimuli of liver fibrosis. The actions of leptin are mediated via hepatic stellate cell activation, and liver fibrosis occurs through its indirect effect on the Kupffer cells. Moreover, it regulates the phosphoinositide 3-kinase/protein kinase B (PI-3K/Pkt) pathway, which plays an essential step in the cell motility, proliferation, survival, and angiogenesis in tumor cells including Hepatocellular Carcinoma (HCC). Thus, leptin can promote HCC proliferation, migration, and invasion. Aim of Study: The present study aimed to evaluate the diagnostic and prognostic value of serum Leptin as a tumor marker in Hepatocellular Carcinoma (HCC) in comparison to Alpha-Fetoprotein (AFP). Subjects and Methods: This study included 180 Egyptian patients that were divided into 4 groups (Group 1: 60 patients with untreated HCC, Group 2: 60 patients with treated HCC, Group 3: 30 patients with end-stage chronic liver disease without HCC) in addition to Group 4: 30 age-matched healthy subjects serving as a healthy control group. All patients and controls were subjected to full history, clinical examination, laboratory investigation, and abdominal ultrasonography (U/S). Serum leptin and alpha-fetoprotein were assayed by using Enzyme-Linked Immunosorbent Assay (ELISA) tech-nique. Results: The results of the present study revealed that serum leptin levels were significantly increased in all the patients' groups when compared to controls; besides, it was significantly higher in untreated and treated HCC patients groups when compared to patient’s group without HCC.Furthermore, serum leptin levels were significantly higher in the patients group with untreated HCC compared to the treated HCC patients group with positive correlation with AFP. Conclusion: AFP was more sensitive and specific in differentiation between cirrhotic patients with or without HCC than Leptin. However, Leptin has a good sensitivity and specificity in differentiating between untreated and treated HCC patients, and it is superior to AFP in the specificity of the differentiation between these two categories. Therefore, serum leptin can be used as a useful screening marker for the diagnosis and prognosis of HCC patients combined with Alfa fetoprotein.

Antibacterial and immunoregulatory activity of a novel hepcidin homologue in diploid hybrid fish (Carassius auratus cuvieri ♀ × Carassius auratus red var ♂)

Hepcidin, a multifunctional hormone oligopeptide, not only exhibits a regulatory role in iron metabolism, but also participates in the regulation of teleostean immunity. In this study, ORF sequence of WR-hepcidin was 258 bp and encoded 85 amino acid residues. Tissue-specific analysis revealed that the highest expression of WR-hepcidin was observed in liver. Aeromonas hydrophila challenge can sharply increased WR-hepcidin mRNA expression in liver, trunk kidney and spleen. The purified WR-hepcidin fusion peptide can directly bind to A. hydrophila and Streptococcus agalactiae, reduce the relative bacterial activity, limit bacterial growth and attenuate their dissemination to tissues in vivo. In addition, the treatment of WR-hepcidin fusion protein can diminish the production of pro-inflammatory cytokines. These results indicated that WR-hepcidin can play a negative regulatory role in bacteria-stimulated pro-inflammatory cytokines production and MyD88-IRAK4 activation.

Acylated and unacylated ghrelin relieve cancer cachexia in mice through multiple mechanisms.

Cancer cachexia is a wasting syndrome resulting from decreased protein synthesis and increased protein degradation. Calpain-dependent cleavage of myofilament is the initial step of myofilament degradation and plays a critical role in muscle atrophy. Ghrelin is a multifunctional hormone known to improve protein synthesis and inhibit protein degradation. However, its mechanism of action is not fully understood. Here we investigated whether acylated ghrelin (AG) and unacylated ghrelin (UnAG) could protect against cancer cachexia in mice bearing CT26 colorectal adenocarcinoma. We found for the first time that both AG and UnAG could inhibit calpain activity in skeletal muscle of cancer cachectic mice. AG and UnAG also improved tumor-free body weight, grip strength, muscle mass, epididymal fat mass, and nutritional state in tumor-bearing (TB) mice. Moreover, AG and UnAG reduced serum tumor necrosis factor-± concentration, increased Akt activity, and downregulated atrogin-1 expression in TB mice. Our results may contribute to the development of an AG/UnAG-based therapy for cancer cachexia.

Thidiazuron-induced efficient biosynthesis of phenolic compounds in callus culture of Ipomoea turbinata Lagasca and Segura

Ipomoea turbinata Lagasca and Segura (Purple Moonflower) belongs to the largest flowering genus Ipomoea in the Convolvulaceae family. Ipomoea turbinata has not been previously explored for its in vitro potential. This is the first study focused on thidiazuron-induced callus culture for efficient biosynthesis of commercially important phenolic compounds in this plant species. Among the two plant growth regulators tested on leaf, stem, and root explants, 5 mg L−1 thidiazuron (TDZ) induced the highest biomass accumulation (61.4 g L−1 fresh weight, 6.3 g L−1 dry weight) in leaf-derived callus cultures after 5 wk of culture. The highest total phenolic and flavonoid contents recorded were 9.04 mg g−1 and 1.16 mg g−1, respectively, in optimized callus cultures. High-performance liquid chromatography analysis indicated high levels of pharmacologically important anticancer compounds such as chlorogenic acid (13.48 mg g−1), arctigenin (11.67 mg g−1), quercetin (6.19 mg g−1), and kaempferol (5.48 mg g−1), along with other phenolic acids. Furthermore, the antioxidant activity was also evaluated, and leaf-derived callus culture displayed a maximum of 62.6% antioxidant potential. The induction of improved biomass accumulation in callus culture and the production of multipotent bioactive metabolites shows the potential of the multifunctional thidiazuron hormone as an efficient elicitation tool in callus culture of I. turbinata.

Vitamin D Attenuates Oxidative Damage and Inflammation in Retinal Pigment Epithelial Cells

Age-related macular degeneration (AMD), the most common visual disorder in elderly people, is characterized by the formation of deposits beneath the retinal pigment epithelium (RPE) and by dysfunction of RPE and photoreceptor cells. The biologically active form of vitamin D, 1,25-(OH)2D3 (VITD), is categorized as a multifunctional steroid hormone that modulates many transcriptional processes of different genes and is involved in a broad range of cellular functions. Epidemiological and genetic association studies demonstrate that VITD may have a protective role in AMD, while single nucleotide polymorphisms in the vitamin D metabolism gene (CYP24A1) increase the risk of AMD. However, the functional mechanisms of VITD in AMD are not fully understood. In the current study, we investigated the impact of VITD on H2O2-induced oxidative stress and inflammation in human RPE cells. We demonstrate that exposure to H2O2 caused significantly reduced cell viability, increased production of reactive oxygen species (ROS), lowered expression of antioxidant enzymes and enhanced inflammation. VITD exposure notably counteracted the above H2O2-induced effects. Our data suggest that VITD protects the RPE from oxidative damage and elucidate molecular mechanisms of VITD deficiency in the development of AMD.

Ethylene Biosynthesis, Signaling, and Crosstalk with Other Hormones in Rice

AbstractEthylene is a multifunctional hormone involved in regulating plant development, conferring adaptive growth, and responding to biotic/abiotic stresses. Rice is a monocotyledonous crop and usually grows in water environments with some unique features. Here, ethylene biosynthesis, signaling, and interaction with other hormones in rice are summarized and discussed in comparison to those from Arabidopsis and/or other plants. Ethylene biosynthesis in rice responds to internal developmental signals and external stimuli such as grain filling, leaf senescence, darkness, mechanical resistance, hypoxia, chill, salt stress, and metal ions. Gene expression regulation in ethylene biosynthesis pathway shows time and spatial specificity. Through mutant analysis and homologue analysis, an ethylene signaling pathway is proposed in rice, and conserved components/mechanisms as well as new components/mechanisms are identified. Ethylene widely interacts with other hormones in rice by synergy or antagonism. Normally, auxin and gibberellin are synergistic with ethylene to regulate growth, while abscisic acid is antagonistic to ethylene in reproductive growth and various stress response. Ethylene diminishes jasmonic acid–inhibited elongation growth, but synergistically promotes leaf senescence. All these studies provide novel insights into the ethylene biology in rice and other crops, and may facilitate breeding for cultivars with better agronomic traits.

Mitofusin 2 Is Essential for IP3-Mediated SR/Mitochondria Metabolic Feedback in Ventricular Myocytes.

Aim: Endothelin-1 (ET-1) and angiotensin II (Ang II) are multifunctional peptide hormones that regulate the function of the cardiovascular and renal systems. Both hormones increase the intracellular production of inositol-1,4,5-trisphosphate (IP3) by activating their membrane-bound receptors. We have previously demonstrated that IP3-mediated sarcoplasmic reticulum (SR) Ca2+ release results in mitochondrial Ca2+ uptake and activation of ATP production. In this study, we tested the hypothesis that intact SR/mitochondria microdomains are required for metabolic IP3-mediated SR/mitochondrial feedback in ventricular myocytes.Methods: As a model for disrupted mitochondrial/SR microdomains, cardio-specific tamoxifen-inducible mitofusin 2 (Mfn2) knock out (KO) mice were used. Mitochondrial Ca2+ uptake, membrane potential, redox state, and ATP generation were monitored in freshly isolated ventricular myocytes from Mfn2 KO mice and their control wild-type (WT) littermates.Results: Stimulation of ET-1 receptors in healthy control myocytes increases mitochondrial Ca2+ uptake, maintains mitochondrial membrane potential and redox balance leading to the enhanced ATP generation. Mitochondrial Ca2+ uptake upon ET-1 stimulation was significantly higher in interfibrillar (IFM) and perinuclear (PNM) mitochondria compared to subsarcolemmal mitochondria (SSM) in WT myocytes. Mfn2 KO completely abolished mitochondrial Ca2+ uptake in IFM and PNM mitochondria but not in SSM. However, mitochondrial Ca2+ uptake induced by beta-adrenergic receptors activation with isoproterenol (ISO) was highest in SSM, intermediate in IFM, and smallest in PNM regions. Furthermore, Mfn2 KO did not affect ISO-induced mitochondrial Ca2+ uptake in SSM and IFM mitochondria; however, enhanced mitochondrial Ca2+ uptake in PNM. In contrast to ET-1, ISO induced a decrease in ATP levels in WT myocytes. Mfn2 KO abolished ATP generation upon ET-1 stimulation but increased ATP levels upon ISO application with highest levels observed in PNM regions.Conclusion: When the physical link between SR and mitochondria by Mfn2 was disrupted, the SR/mitochondrial metabolic feedback mechanism was impaired resulting in the inability of the IP3-mediated SR Ca2+ release to induce ATP production in ventricular myocytes from Mfn2 KO mice. Furthermore, we revealed the difference in Mfn2-mediated SR-mitochondrial communication depending on mitochondrial location and type of communication (IP3R-mRyR1 vs. ryanodine receptor type 2-mitochondrial calcium uniporter).

Chemical synthesis and characterization of a new quinazolinedione competitive antagonist for strigolactone receptors with an unexpected binding mode.

Strigolactones (SLs) are multifunctional plant hormones regulating essential physiological processes affecting growth and development. In vascular plants, SLs are recognized by α/β hydrolase-fold proteins from the D14/DAD2 (Dwarf14/Decreased Apical Dominance 2) family in the initial step of the signaling pathway. We have previously discovered that N-phenylanthranilic acid derivatives (e.g. tolfenamic acid) are potent antagonists of SL receptors, prompting us to design quinazolinone and quinazolinedione derivatives (QADs and QADDs, respectively) as second-generation antagonists. Initial in silico docking studies suggested that these compounds would bind to DAD2, the petunia SL receptor, with higher affinity than the first-generation compounds. However, only one of the QADs/QADDs tested in in vitro assays acted as a competitive antagonist of SL receptors, with reduced affinity and potency compared with its N-phenylanthranilic acid 'parent'. X-ray crystal structure analysis revealed that the binding mode of the active QADD inside DAD2's cavity was not that predicted in silico, highlighting a novel inhibition mechanism for SL receptors. Despite a ∼10-fold difference in potency in vitro, the QADD and tolfenamic acid had comparable activity in planta, suggesting that the QADD compensates for lower potency with increased bioavailability. Altogether, our results establish this QADD as a novel lead compound towards the development of potent and bioavailable antagonists of SL receptors.

Metabolic stress leads to divergent changes in the ghrelinergic system in goldfish (Carassius auratus) gonads

Various endocrine factors that regulate energy homeostasis are also implicated in the reproductive physiology of mammals. However, the hormonal link between metabolism and reproduction in fish is poorly understood. Ghrelin is a multifunctional hormone with both metabolic and reproductive roles in vertebrates. Post-translational acylation by ghrelin-O-acyltransferase (GOAT) is critical for its biological actions. The expression of ghrelin, ghrelin or growth hormone secretagogue receptor (GHSR), and GOAT (which forms the ghrelinergic system) in fish under metabolic stress remains unclear. In this research, we used RT-qPCR and Western blot analysis to determine the expression of the ghrelinergic system in goldfish (during the reproductively active phase) hypothalamus and gonads under 7 and 28 days of fasting. We found a significant increase in preproghrelin mRNA expresson in the ovary, and GOAT mRNA expression in the testis of goldfish deprived of food for 7 days. In fish deprived of food for 28 days, preproghrelin, GHSR and GOAT mRNA expression was significantly increased in the hypothalamus of male goldfish. Such differences were not observed in the hypothalamus of female fish, and in the testis of 28 days fasted fish. Meanwhile, preproghrelin, GHSR, and GOAT expression (both mRNA and protein) was significantly increased in the ovary of female fish fasted for 28 days. Ghrelin has been shown to suppress oocyte maturation in fish. The upregulation of a system that has ovarian inbititory roles suggests a role for ghrelin in maintaining reduced reproductive capability during metabolically challenging periods.

Ghrelin Physiology and Pathophysiology: Focus on the Cardiovascular System

Ghrelin is a multifunctional peptide hormone, mainly synthesized by P / D1 cells of the stomach fundus mucosa. Its basic effect, whichis realized via GHS-R1 α receptor in the arcuate and the ventromedial nucleuses of hypothalamus, is stimulation of the synthesis of pituitaryhormones. Ghrelin is involved in control of appetite and energy balance, regulation of carbohydrate and lipid metabolism, cellproliferation and apoptosis, as well as modulation of functioning of gastrointestinal, cardiovascular, pulmonary and immune systems.It was found that cardiomyocytes are able to synthesize ghrelin. High concentrations of GHS-R1α in the heart and major blood vesselsevidence for its possible participation in functioning of cardiovascular system. Ghrelin inhibits apoptosis of cardiomyocytes andendothelial cells, and improves the functioning of the left ventricle (LV) after injury of ischemia-reperfusion mechanism. In rats withheart failure (HF) ghrelin improves LV function and attenuates development of cardiac cachexia. In addition, ghrelin exerts vasodilatoryeffects in humans, improves cardiac function and reduces peripheral vascular resistance in patients with chronic HF. The reviewcontains of the predictive value of ghrelin in the development and prevention of cardiovascular disease.

The Role of Vitamin D in Implant Success

Vitamin D is a multifunctional hormone that is mostly produced in the skin following exposure to ultraviolet B sunlight. It coordinates the physiological functions by controlling calcium and phosphate metabolism, promotes growth, and induces necessary remodeling of the bones and teeth. As known high serum vitamin D levels have beneficial effects on oral health and that exposure to safe sunlight can reduce the risk of periodontal disease and thus affect implant success. In order to prove this hypothesis, we conducted a detailed literature review. In the literature review, 3 clinical studies and 2 case reports of implant and vitamin D were found. Although vitamin D is highly correlated with bone metabolism, and expected a very close relationship with implant success, a large number of experimental studies and few clinical studies unfortunately showed contradictory results and no direct studies showing vitamin D and implant success were found. Therefore, it is necessary to demonstrate the existence or absence of this relationship by conducting much broader studies.

Ghrelin and male reproduction

Ghrelin is a multifunctional peptide hormone, conventionally known to be secreted by the stomach. The synthesis of ghrelin by the reproductive organs signifies its autocrine and/or paracrine actions upon the gonads. Expression of the functional ghrelin receptor is observed in different levels of the hypothalamic-pituitary-gonadal axis, suggesting its action on hypothalamic secretion of gonadotropin-releasing hormone and the pulsatile secretion of pituitary gonadotropins. It mainly acts to inhibit the secretion of the luteinizing hormone and thereby may also hinder proper testicular functions. This review article aims to provide a concise concept on (a) the characteristics, secretion and mode of actions of ghrelin, and (b) the role of ghrelin as a potential regulator of male reproductive functions. It may act upon the hypothalamic-pituitary-gonadal axis as well as directly regulate key testicular functions such as testosterone secretion, Leydig cell proliferation and expressions of prime functional proteins in the seminiferous tubule. These actions of ghrelin on testicular functions appear to be species-specific. Ghrelin and its versatile biological functions bring to a consensus that further research on ghrelin may establish one of the associations between body energy status with alterations in male reproductive functions.

Circulating prolactin concentrations and risk of type 2 diabetes in US women.

Prolactin, a multifunctional hormone, is involved in regulating insulin sensitivity and glucose homeostasis in experimental studies. However, whether circulating concentrations of prolactin are associated with risk of type 2 diabetes remains uncertain. We analysed the prospective relationship between circulating prolactin concentrations and type 2 diabetes risk in the Nurses' Health Study (NHS) and NHSII with up to 22years of follow-up. Total plasma prolactin was measured using immunoassay in 8615 women free of type 2 diabetes and cardiovascular disease at baseline blood collection (NHS 1989-1990; NHSII 1996-1999) and a subset of 998 NHS women providing a second blood sample during 2000-2002. Baseline bioactive prolactin was measured in a subset of 2478 women using the Nb2 bioassay. HRs were estimated using Cox regression. A total of 699 incident type 2 diabetes cases were documented during 156,140 person-years of follow-up. Total plasma prolactin levels were inversely associated with type 2 diabetes risk; the multivariable HR comparing the highest with the lowest quartile was 0.73 (95% CI 0.55, 0.95; ptrend = 0.02). The associations were similar by menopausal status and other risk factors (pinteraction > 0.70). Additional adjustment for sex and growth hormones, adiponectin, and inflammatory and insulin markers did not significantly alter the results. The association of plasma bioactive prolactin with type 2 diabetes risk was non-significantly stronger than that of total prolactin (HR comparing extreme quartiles, 0.53 vs 0.81 among the subset of 2478 women, pdifference = 0.11). The inverse association of total prolactin with type 2 diabetes was significant during the first 9years after blood draw but waned linearly with time, whereas for bioactive prolactin, the inverse relationship persisted for a longer follow-up time after blood draw. A normally high circulating total prolactin concentration was associated with a lower type 2 diabetes risk within 9-10years of follow-up since blood draw in US women. Our findings are consistent with experimental evidence, suggesting that among healthy women, prolactin within the biologically normal range may play a protective role in the pathogenesis of type 2 diabetes.