Livio Casarini

Livio Casarini
Università degli Studi di Modena e Reggio Emilia | UNIMO · Department of Biomedical, Metabolical and Neurosciences

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Introduction
Livio Casarini currently works at the Department of Biomedical, Metabolical and Neurosciences, Università degli Studi di Modena e Reggio Emilia. Livio does research in Reproductive Endocrinology and Clinical Pharmacology. Their most recent publication is 'Probing the effect of sildenafil on Progesterone and Testosterone production by an intracellullar FRET/BRET combined approach'.
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Research items (86)
Article
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Recombinant follicle-stimulating hormone (FSH) (follitropin alfa) and biosimilar preparations are available for clinical use. They have specific FSH activity and a unique glycosylation profile dependent on source cells. The aim of the study is to compare the originator (reference) follitropin alfa (Gonal-f®)- with biosimilar preparations (Bemfola®...
Article
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Context. Post-finasteride syndrome (PFS) occurs in patients with androgenic alopecia after suspension of the finasteride treatment, leading to a large variety of persistent side effects. Despite the severity of the clinical picture, the mechanism underlying the PFS symptoms onset and persistence is still unclear. Objective. To study whether epigene...
Article
Full-text available
The glycoprotein follicle-stimulating hormone (FSH) acts on gonadal target cells, hence regulating gametogenesis. The transduction of the hormone-induced signal is mediated by the FSH-specific G protein-coupled receptor (FSHR), of which the action relies on the interaction with a number of intracellular effectors. The stimulatory Gαs protein is a l...
Article
Förster Resonance Energy Transfer (FRET)-based biosensors have been recently applied to the study of biological pathways. In this study, a new biosensor was validated for the first time in live HEK293 and steroidogenic MLTC-1 cell line for studying the PDE5 inhibitor effect on hCG/LH-induced steroidogenic pathway. The sensor benefits of FRET betwee...
Article
Growth Hormone (GH) deficiency is frequent in HIV-infected patients treated with antiretroviral therapy. We treated GH3 cells with antiretrovirals (nevirapine, ritonavir or abacavir sulfate; 100 pM-1 mM range), after transfection with human growth hormone releasing hormone (GHRH) receptor cDNA. Cells viability, intracellular cAMP, phosphorylation o...
Article
Research question: What is the cumulative effect of two follicle-stimulating hormone receptor (FSHR) mutations in spontaneous ovarian hyperstimulation syndrome (sOHSS) pathogenesis? Are these mutations in the mono- or biallelic state? Design: Two FSHR mutations were found in a pregnant patient affected by sOHSS with no predisposing conditions. Whil...
Article
Pituitary gonadotropins, follicle-stimulating (FSH) and luteinizing hormone (LH), promote follicular recruitment and support antral follicle growth, maturation and selection, resulting in ovulation of the dominant follicle. FSH and LH biological functions are mediated by G protein-coupled receptors, FSHR and LHCGR, resulting in the activation of a...
Article
Luteinizing hormone (LH) and chorionic gonadotropin (CG) are glycoproteins fundamental for sexual development and reproduction. Since they act on the same receptor (LHCGR), there is a general consensus that LH and hCG are equivalent. However, separate evolution of LHβ and hCGβ subunits occurred in primates, resulting in two molecules sharing ∼85% i...
Article
Infertility treatment may represent a paradigmatic example of precision medicine. Follicle-stimulating hormone (FSH) has been proposed as a valuable therapeutic option both in males and in females, even if a standardized approach is far to be established. To date, several genetic mutations as well as polymorphisms have been demonstrated to signific...
Article
It is common opinion that maximal activation of luteinizing hormone (LH)-dependent steroidogenic signal occurs at <1% of human LH/choriogonadotropin (hCG) receptor (LHCGR) occupancy. This effect would be a consequence of an excess of receptors expressed on the surface of theca cells, resulting in a pool of LHCGRs remaining unbound (spare). This con...
Article
Full-text available
Background Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) are glycoprotein hormones regulating development and reproductive functions by acting on the same receptor (LHCGR). We compared the LH and hCG activity in gonadal cells from male mouse in vitro, i.e. primary Leydig cells, which is a common tool used for gonadotropin bioassay...
Article
Full-text available
Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) have been considered biologically equivalent because of their structural similarities and their binding to the same receptor; the LH/CGR. However, accumulating evidence suggest that LH/CGR differentially responds to the two hormones triggering differential intracellular signaling and s...
Article
Study question: Are four urinary hCG/menotropin (hMG) and one recombinant preparation characterized by different molecular features and do they mediate specific intracellular signaling and steroidogenesis? Summary answer: hCG and hMG preparations have heterogeneous compositions and mediate preparation-specific cell signaling and early steroidoge...
Article
Reproduction is a fundamental process for the species maintenance and the propagation of genetic information. The energy expenditure for mating is overtaken by motivational stimuli, such as orgasm, finely regulated by steroid hormones, gonadotropins, neurotransmitters and molecules acting in the brain and peripheral organs. These functions are ofte...
Article
Setting Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) act on the same receptor, activating different signal transduction pathways. The role of LH or hCG addition to follicle-stimulating hormone (FSH) as well as menopausal gonadotropins (human menopausal gonadotropin; hMG) in controlled ovarian stimulation (COS) is debated. Object...
Data
Forrest plot evaluating the pregnancy rate comparing follicle-stimulating hormone to human menopausal gonadotropin in in vitro fertilization/intracytoplasmic injection protocols alone, using gonadotropin-releasing hormone agonist.
Data
Forrest plot evaluating the pregnancy rate comparing follicle-stimulating hormone to human menopausal gonadotropin in in vitro fertilization/intracytoplasmic injection protocols alone.
Article
Full-text available
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are glycoprotein hormones used for assisted reproduction acting on the same receptor (LHCGR) and mediating different intracellular signaling. We evaluated the pro-and anti-apoptotic effect of 100 pM LH or hCG, in the presence or in the absence of 200 pg/mL 17β-estradiol, in long-term,...
Article
Several controlled ovarian stimulation (COS) protocols were developed to increase yield of mature oocytes to be retrieved in assisted reproductive techniques (ART). Ovarian reserve (OR) influences the COS response and it represents the main parameter helping clinicians in refining clinical treatments, in the perspective of a “personalized” ART. Thi...
Article
We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm c...
Chapter
Full-text available
The two gonadotrophin receptors (GnRs), luteinizing hormone receptor (LHCGR) and follicle-stimulating receptor (FSHR), belong to the glycoprotein hormone receptor subgroup of type A G protein-coupled receptors (GPCRs). LHCGR binds specifically the two structurally similar gonadotrophins, luteinizing hormone (LH) and human chorionic gonadotrophin (h...
Article
Background: VDR and AHR are nuclear receptors, which exert their function through binding with ligands and formation of a molecular complex. These complexes translocate to the nucleus and activate the expression of a series of genes with a responsive element to VDR or AHR. Both receptors have been identified to play a role in the pathogenesis of en...
Chapter
Gonadotropins (LH, FSH, and hCG) act in concert in the regulation of female reproductive system. Exploiting this influence, they are part of the assisted reproductive technique protocols. In this review we analyze the effectiveness of the different available gonadotropin formulations and the consequent adverse events. Moreover, different protocols...
Article
Gonadotropin signaling classically involves proliferative, steroidogenic and apoptotic stimuli. In this study, we used the human granulosa cell line hGL5 to demonstrate how follicle-stimulating hormone (FSH) and luteinizing hormone (LH) differently control proliferative or apoptotic signals, revealing novel intrinsic properties of their receptors (...
Article
Background: Luteinizing hormone (LH) and choriogonadotropin (hCG) are glycoprotein hormones regulating ovarian function and pregnancy. They were routinely used in assisted reproduction techniques (ART) assuming they are equivalent, due to their binding to a common receptor (LHCGR). However, differences between LH and hCG were demonstrated at molecu...
Article
Human luteinizing hormone (LH) and human choriogonadotropin (hCG) were considered biologically equivalent for decades due to structural similarities and binding to the same receptor (LHCGR). However, LHCGR triggers differential, LH- and hCG-specific, cAMP production, steroidogenesis, ERK and AKT activation and gene expression in granulosa cells. Be...
Article
Several studies have attempted to explain the high overall prevalence of polycystic ovary syndrome among women worldwide (about 4–10%) despite its link to subfertile phenotypes. For this reason, it is considered an evolutionary paradox. In this review, we show that several genetic loci associated with the disease differently modulate the reproducti...
Chapter
The two gonadotrophin receptors (GnRs), luteinizing hormone receptor (LHCGR) and follicle-stimulating receptor (FSHR), belong to the glycoprotein hormone receptor subgroup of type A G protein-coupled receptors (GPCRs). LHCGR binds specifically the two structurally similar gonadotrophins, luteinizing hormone (LH) and human chorionic gonadotrophin (h...
Article
Luteinizing hormone (LH) and choriogonadotropin (hCG) are glycoprotein hormones regulating ovarian function and pregnancy, respectively. Since these molecules act on the same receptor (LHCGR), they were traditionally assumed as equivalent in assisted reproduction techniques (ART), although differences between LH and hCG were demonstrated at molecul...
Article
Full-text available
Gonadotropins and their receptors' genes carry several single-nucleotide polymorphisms resulting in endocrine genotypes modulating reproductive parameters, diseases and lifespan leading to important implications for reproductive success and potential relevance during human evolution. Here we illustrate common genotypes of the gonadotropins and gona...
Article
Background: The immortalised human granulosa cell line (hGL5) is not responding to gonadotropins, which fail to activate the cAMP/PKA/CREB pathway, progesterone production, cell rounding and apoptosis, suggesting that FSH- and LH/hCG-receptors (FSHR; LHCGR) are downregulated. Aim: To investigate whether the mechanism of FSHR/LHCGR downregulation is...
Article
Full-text available
Context: Polycystic ovary syndrome (PCOS) is a common female endocrine disorder characterized by phenotypes ranging from hyperandrogenism to metabolic disorders, more prevalent in people of African/Caucasian and Asian ancestry. Because PCOS impairs fertility without diminishing in prevalence, it was considered an evolutionary paradox. Genome-Wide A...
Article
The single nucleotide polymorphism p.N680S of the follicle-stimulating hormone (FSH) receptor (FSHR) is a discrete marker of ovarian response but previous in vitro studies failed to demonstrate differences in the response to FSH between N and S carrier cells. Here we demonstrate that p.N680S mediates different kinetics of the response to FSH in vit...
Article
Full-text available
Background: Thyroidectomized patients need variable doses of levothyroxine (LT4) to obtain target thyroid-stimulating hormone (TSH) levels. Individual feedback set-points have been hypothesized and the influence of several genes in the regulation of the pituitary-thyroid axis has been demonstrated. Objectives: We hypothesized that genetic varian...
Article
This chapter presents an overview of the gene polymorphisms underlying the functions of ovarian receptors and their clinical implications in the female fecundity. A selection of genetic studies revealing significant associations between receptor polymorphisms, gene mutations, and some pathological conditions (i.e., female infertility, premature ova...
Article
Introduction: PCOS is a common endocrine disorder in women exhibiting characteristics ranging from hyperandrogenic to metabolic phenotypes, more prevalent in people of African/Caucasian and Asian ancestry, respectively. Since PCOS impairs fertility without diminishing in prevalence, it was discussed as an evolutionary paradox. GWAS identified 17 SN...
Article
To assess the potential pharmacogenetic use of FSH for infertility treatment. Review of the literature and genomic databases. SNP assessed: rs6166 (c.2039A>G, p.N680S), rs6165 (c.919A>G, p.T307A), rs1394205 (c.-29G>A) in FSHR and rs10835638 (c.-211G>T) in FSHB. Literature search via PubMed. Blast analysis of genomic information available in the NCB...
Article
Full-text available
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with a steadily increasing incidence in the last few decades worldwide. The predisposition to developing this carcinoma by the heterozygous state of rs2910164 within the precursor of the miR-146a has been reported, but recently not confirmed. Interestingly, on the same chrom...
Article
Since gonadotropins are the fundamental hormones that control ovarian activity, genetic polymorphisms may alter gonadal responsiveness to glycoproteins; hence they are important regulators of hormone activity at the target level. The establishment of the pool of primordial follicles takes place during fetal life and is mainly under genetic control....
Article
Full-text available
Human luteinizing hormone (hLH) and chorionic gonadotropin (hCG) act on the same receptor (LHCGR) but it is not known whether they elicit the same cellular and molecular response. This study compares for the first time the activation of cell-signalling pathways and gene expression in response to hLH and hCG. Using recombinant hLH and recombinant hC...
Data
Recovery of hGLC response to hLH and hCG, over 0–6 days from in vivo pick-up. Total cAMP measured on the (a) third and (b) sixth day of culture are shown. (TIF)
Data
Comparison between recombinant and extractive gonadotropin effect on ERK1/2 and AKT phosphorylation. Dose-response experiment evaluating the maximal phospho-ERK1/2 and phospho-AKT activation in hGL5/LHCGR by Western blotting. The cells were stimulated for 15 minutes by different recombinant or extractive hLH or hCG doses and the phospho-ERK1/2 and...
Data
Dose-response and time-course experiments in hGLC. a. Dose-response experiment with r-hLH and r-hCG in hGLC in the presence of 500 µM IBMX. Total cAMP was measured after 3 hours. One of three independent experiments is shown. b. Time-course experiment performed by continuous incubation of hGLC for different time-points in the presence of 500 µM IBM...
Data
Western blot analysis of phospho ERK1/2 (a) and phospho AKT (b) and efficacy of the relative inhibitors U0126 and LY294002 in hGLC stimulated for 15 with hLH or hCG. (TIF)
Data
Intracellular cAMP production over 6 hours in hGLC stimulated by hLH (500 pM) or hCG (100 pM). Each value was normalized vs unstimulated. One representative experiment of two is shown. (TIF)
Data
Control samples of immunofluorescence analysis. Non-permeabilized cells control of LHCGR sequestration from cell surface in hLH-treated hGLC, after 15 hours. a. Unstimulated cells. b. hLH-treated hGLC. LHCGR is labeled in red (Tritc), the cytoplasmic marker ERK1/2 in green (Fitch) and cell nuclei marker (DAPI) in blue. The merging of the three imag...
Data
Comparison between recombinant and extractive gonadotropins effects on total cAMP production. a. Dose-response experiment with r-hLH and r-hCG versus ex-hLH and ex-hCG in COS7/LHCGR, in the presence of 500 µM IBMX. Total cAMP was measured after 3 hours. One representative experiment is shown. b. The experiment shown in panel “a” has been repeated u...
Article
Background: Previous analysis of aromatase gene and protein expression in peripheral blood leucocytes (PBLs), studied in children and adults, was extended to elderly subjects. In addition, we assessed whether aromatase expression in PBLs could be used as a parameter of aromatase expression in other tissues, using the cynomolgus monkey as model. M...
Conference Paper
Full-text available
Background / Purpose: Patients thyroidectomized for thyroid cancer need variable doses of levothyroxine (LT4) to obtain thyroid stimulating hormone (TSH) suppression. A predetermined thyroid function set-point for each individual has been hypothesized, suggesting a genetic influence in the regulation of pituitary-thyroid axis. We hypothesized tha...
Article
Gonadotropins, the action of which is mediated at the level of their gonadal receptors, play a key role in sexual development, reproductive functions and in metabolism. The involvement of the gonadotropins and their receptor genotypes on reproductive function are widely studied. A large number of gonadotropins and their receptors gene polymorphisms...
Article
The study was designed to evaluate in vitro the cellular mechanisms of the single nucleotide polymorphism (SNP) p.N680S of the FSH receptor gene (FSHR) in human granulosa cells (GC) and included patients homozygous for the FSHR SNP (NN/SS) undergoing ovarian stimulation. GC were isolated during oocyte retrieval and cultured for 1–7 days. Basal oest...
Article
The present investigation examines the effects of the marine toxins, okadaic acid (OA) and palytoxin (PTX), on some genes involved in the neural and muscular specification and patterning of Xenopus laevis. The RT-PCR analyses performed at different stages of embryonic and larval development (stages 11-47) demonstrated that both toxins induce an ove...
Article
The FETAX (frog embryo teratogenesis assay Xenopus) is considered a useful bioassay to detect health hazard substances. In the study of the marine toxin palytoxin (PTX), FETAX has revealed evident impacts on embryo mortality, teratogenesis and growth at the two highest (370 and 37nM) concentrations used. Significant mortality rates, peaks in the nu...
Article
Full-text available
Given the ecological and economic importance of bivalve molluscs, the evaluation of their welfare is one of the primary aims for both biologists and people working in shell fishing. After a three year-long period monitoring the cytotoxic activity exerted by the hemolymph from the mussel Mytilus galloprovincialis, we have concluded that cytotoxicity...
Article
The present study analyzes the effects of the marine toxins okadaic acid (OA) and palytoxin (PTX) on the phagocytic activity of immunocytes from the mussel Mytilus galloprovincialis. In particular, we describe how the effects of the two biotoxins are influenced by the temperature and experimental stress applied before hemolymph withdrawal. The coll...
Article
The present study investigates the effects on immune-related parameters of various stress factors (air exposure, mechanical stress, high temperature and extreme salinity conditions) faced by the bivalve mollusc Mytilus galloprovincialis during marketing procedures. We observed that some stress typologies increase phagocytosis and the number of circ...
Article
The Frog Embryo Teratogenesis Assay Xenopus (FETAX), is a screening assay using embryos at gastrula stage of the anuran Xenopus laevis to identify substances that may pose a developmental hazard in humans. The FETAX assay evaluates three parameters, i.e. mortality, delayed growth and embryo malformation. In the present investigation, the FETAX prot...