A5004035589- Hypothalamic control of reproductive hormones
- Adrenal and Paraganglionic Tumors
- Hormonal Regulation and Hypertension
- Cancer, Hypoxia, and Metabolism
- Sexual Differentiation and Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Ovarian function and disorders
- Growth Hormone and Insulin-like Growth Factors
- Plant Reproductive Biology
- Genetic Syndromes and Imprinting
- Reproductive Biology and Fertility
- Hormonal and reproductive studies
- Estrogen and related hormone effects
- Pituitary Gland Disorders and Treatments
- Adrenal Hormones and Disorders
- Sperm and Testicular Function
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Neuroblastoma Research and Treatments
- Nuclear Structure and Function
- Regulation of Appetite and Obesity
- Ovarian cancer diagnosis and treatment
- Testicular diseases and treatments
- Birth, Development, and Health
- RNA Research and Splicing
Universidade de São Paulo
2016-2025
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2016-2025
Hospital de Clínicas de Porto Alegre
2023-2025
WiLAN (Canada)
2024
Universidade Cidade de São Paulo
2024
Hospital de Clínicas
1997-2022
Instituto do Câncer do Estado de São Paulo
2018
Hospital São Paulo
2007-2017
Laboratory of Molecular Genetics
2016
Institute of Developmental Physiology
2016
Gonadotropin-dependent, or central, precocious puberty is caused by early maturation of the hypothalamic-pituitary-gonadal axis. In girls, this condition most often idiopathic. Recently, a G protein-coupled receptor, GPR54, and its ligand, kisspeptin, were described as an excitatory neuroregulator system for secretion gonadotropin-releasing hormone (GnRH). study, we have identified autosomal dominant GPR54 mutation--the substitution proline arginine at codon 386 (Arg386Pro)--in adopted girl...
The onset of puberty is first detected as an increase in pulsatile secretion gonadotropin-releasing hormone (GnRH). Early activation the hypothalamic–pituitary–gonadal axis results central precocious puberty. timing pubertal development driven part by genetic factors, but only a few, rare molecular defects associated with have been identified.
The clinical features and natural history of adrenocortical carcinoma are highly dependent on the type center reporting their experience. Observations from oncology services suggest a high incidence nonfunctioning tumors, whereas reports endocrine clinics emphasize excessive corticoid androgen production in majority tumors. rate childhood adrenal generally has been under emphasized.Over past 17 years, authors have evaluated treated 47 patients with referred to University Sao Paulo, 22 whom...
Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R-activating mutation was described in central precocious (CPP).Our objective to investigate patients with idiopathic CPP normosmic IHH.Eighty-three children (77 girls) 61 IHH (40 men) were studied. The control group consisted 200 individuals normal pubertal development.The...
Abstract Context: Mutations in TAC3 and TACR3 (encoding neurokinin B its receptor) have been identified Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations not yet tested genotype-phenotype correlations established. Objective: A broad cohort of normosmic IHH probands was screened for mutations TAC3/TACR3 to evaluate the prevalence such define genotype/phenotype relationships. Design Setting: The study consisted sequencing TAC3/TACR3, vitro functional...
Abstract Context: Central precocious puberty (CPP) results from premature activation of the hypothalamic–pituitary–gonadal axis. Few genetic causes CPP have been identified, with most common being mutations in paternally expressed imprinted gene MKRN3. Objective: To identify etiology a large multigenerational family. Design: Linkage analysis followed by whole-genome sequencing was performed family five female members nonsyndromic CPP. Detailed phenotyping at time initial diagnosis and...
Abstract Disclosure: A.P. Canton: None. C.E. Seraphim: L.R. Montenegro: A. Krepsichi: B.B. Mendonca: Latronico: V.N. Brito: Background: The etiology of central precocious puberty (CPP) has expanded with the identification new genetic causes, including monogenic deficiency MKRN3 in familial cases. Objectives: To assess prevalence CPP causes and predictors involvement this phenotype. Methods: A single-center retrospective cohort study was performed for an etiological survey patients CPP. All...
In normal males, luteinizing hormone (LH) regulates the function of Leydig cells and, hence, male sexual differentiation, pubertal androgenization, function, and fertility. Abnormalities in result primary hypogonadism varying degrees pseudohermaphroditism.1-5 these patients, are absent, hypoplastic, or unresponsive to stimulation with human chorionic gonadotropin (hCG), studies testicular-biopsy samples from some patients have revealed absence LH receptors.2,3 women, stimulates theca produce...
Mutations of the p53 tumor suppressor gene are single most common genetic alterations in human cancers. Recently, a distinct nucleotide substitution was identified exon 10 gene, leading to an Arg337His mutation 97% children with adrenocortical tumors from Southern Brazil. In present study, we investigated presence this larger series 55 patients (37 adults and 18 children) benign malignant sporadic tumors. None had family cancer histories that conformed criteria for Li-Fraumeni syndrome....
Kallmann syndrome (KS) consists of congenital, isolated, idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. The gene responsible for the X-linked form KS, KAL, encodes a protein, anosmin, that plays key role in migration GnRH neurons olfactory nerves to hypothalamus. In addition pedigrees, autosomal dominant recessive kindreds with KS have been reported. relative importance these vs. genes producing frequency KAL mutations, are currently unknown because rare disorders large series...
Selective luteinizing hormone deficiency due to mutations in the beta-subunit gene (LHB) is a rare cause of hypogonadism. We describe clinical features consanguineous family which three siblings, two men and one woman, had hypogonadism related isolated deficiency. These subjects have newly discovered homozygous mutation 5' splice site LHB: IVS2+1G-->C. This disrupts splicing messenger RNA (mRNA), generating gross abnormality processing mRNA, abrogates secretion hormone. also determined that...
Adrenocortical tumors are heterogeneous neoplasms with incompletely understood pathogenesis. IGF-II overexpression has been consistently demonstrated in adult adrenocortical carcinomas.The objective of the study was to analyze expression and its receptor (IGF-IR) pediatric effects a selective IGF-IR kinase inhibitor (NVP-AEW541) on tumor cells.Fifty-seven (37 adenomas 20 carcinomas) from 23 children 34 adults were studied.Gene determined by quantitative real-time PCR. Cell proliferation...
Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic syndromic forms adrenocortical carcinoma (ACC). Abnormal β-catenin staining CTNNB1 mutations are reported to be common both adenoma ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand contribution these tumorigenesis we examined clinicopathological molecular data used mouse models. Evaluation adrenal tumors from 118 adult patients...
Loss-of-function mutations in makorin ring finger 3 (MKRN3), an imprinted gene located on the long arm of chromosome 15, have been recognized recently as a cause familial central precocious puberty (CPP) humans. MKRN3 has potential inhibitory effect GnRH secretion.The objective study was to investigate sequence variations well copy number and methylation abnormalities 15q11 locus patients with apparently sporadic CPP.We studied 215 unrelated children (207 girls eight boys) from three...
Delta-like homolog 1 (DLK1), also called preadipocyte factor 1, prevents adipocyte differentiation and has been considered a molecular gatekeeper of adipogenesis. A DLK1 complex genomic defect was identified in five women from single family with central precocious puberty (CPP) increased body fat percentage.We studied 60 female patients diagnosis CPP or history menarche. Thirty-one them reported puberty. DNA sequencing performed all patients. Serum concentrations were measured using an ELISA...
Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by GnRH deficiency. Several genes have been associated with the pathogenesis of CHH, but most cases still remain without molecular diagnosis. The advent next-generation sequencing (NGS) has allowed simultaneous genotyping several regions, faster, making possible extension genetic knowledge CHH.Genetic characterization large cohort Brazilian CHH patients.A 130 unrelated patients (91 males, 39 females) (75 normosmic 55...
The identification of loss-of-function mutations in MKRN3 patients with central precocious puberty association the decrease expression medial basal hypothalamus mice before initiation reproductive maturation suggests that is acting as a brake on gonadotropin-releasing hormone (GnRH) secretion during childhood. In current study, we investigated mechanism by which prevents premature manifestation pubertal process. We showed that, mice, high rats and nonhuman primates early life, decreases...
The etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital acquired causes that can be associated with structural or functional brain alterations. All CPP culminate in the premature pulsatile secretion hypothalamic GnRH and, consequently, reactivation hypothalamic-pituitary-gonadal axis. activation excitatory factors suppression inhibitory during childhood represent 2 major mechanisms CPP, revealing a delicate balance these opposing neuronal...