Search PubMed⌕ Search

Biomedical subjects

J Gromoll

Publications and source records attributed to J Gromoll.

62 records · Page 4Linked to original sources
PubMed1993

Effects of antiandrogens and ethane dimethane sulphonate (EDS) on gene expression, free subunits, bioactivity and secretion of pituitary gonadotrophins in male rats.

In the male rat, testosterone has been shown to regulate gonadotrophin synthesis and secretion under experimental conditions such as castration or gonadotrophin-releasing hormone (GnRH) antagonist with or without testosterone. The present study aims at clarifying the effects of non-steroidal antiandrogens, Casodex and flutamide, and ethane dimethane sulphonate (EDS) on the regulation of gonadotropin synthesis and secretion. To enable a direct comparison within this study to expected effects of testosterone, a GnRH antagonist-treated group and a castrated group were included. The gene expression of the subunits was correlated with changes in the pituitary and plasma content of immunoreactive luteinizing hormone (LH) and follicle-stimulating hormone (FSH), free subunits and pituitary content of in vitro bioactive LH and FSH. Groups of ten male rats each received the following treatments for 7 days: (1) vehicle; (2) castration; (3) EDS (75 mg/kg); (4) GnRH antagonist (Cetrorelix 250 micrograms/kg/day), (5) Casodex (20 mg/kg/day) or (6) flutamide (20 mg/kg/day). The effectiveness of testosterone deprivation was demonstrated by the reduction of weight in androgen-dependent organs such as epididymides and seminal vesicles in the treated groups. Treatment with flutamide, EDS or castration significantly increased (p < 0.05) serum levels of LH, FSH and alpha-subunit, whereas serum gonadotrophin levels were decreased in the GnRH antagonist-treated group. alpha-Subunit mRNA levels were elevated in the castrated, EDS and flutamide group and LH-beta mRNA levels were increased in the castrated and EDS group. FSH-beta mRNA levels were increased in the castrated group and decreased in the GnRH antagonist group, but remained unchanged in the flutamide and EDS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Antagonists↗
PubMed1992

Molecular cloning of a truncated isoform of the human follicle stimulating hormone receptor.

Northern blot hybridization of human testicular poly (A)+ RNA to a human follicle stimulating hormone receptor probe revealed the existence of multiple mRNA transcripts. In order to investigate whether alternative splicing of the receptor occurs in the human testis we amplified the extracellular and the transmembrane domain of the human testicular follicle stimulating hormone receptor by reverse transcription polymerase chain reaction and subcloned the resulting DNA fragments. Sequence analysis of the recombinant clones revealed the existence of a truncated isoform of the human follicle stimulating hormone receptor which is spliced through a cassette exon mode without a change in the open reading frame, thereby deleting exon IX from the coding region of the receptor.

Amino Acid Sequence↗
PubMed1992

FSH receptor mRNA is expressed stage-dependently during rat spermatogenesis.

In situ hybridization was performed on testicular tissue from adult male Sprague-Dawley rats using cRNA antisense and sense probe of the monkey FSH receptor (FSHR) cDNA to determine the cellular site of synthesis, and possible stage-dependent expression of FSHR mRNA during the cycle of the seminiferous epithelium. Using antisense probe specific binding was first detected in Sertoli cells just prior to sperm release at stage VIII. The strongest specific hybridization signal was found during stages IX and X followed by a decrease of signal intensity in stages XI-XII. No specific binding was found in stages XIII-VII. The sequence of events with the maximum expression of FSHR mRNA in Sertoli cells in stages IX and X, before FSH-binding and FSH-stimulated cAMP production reach maximum values, coincides with a new wave of spermatogenesis and indicates an effect of FSH and spermatogenic cells on the regulation of FSHR mRNA expression.

Animals↗
PubMed1989

Cloning and sequence analysis of cDNA for precursor of a crustacean hyperglycemic hormone.

Crustacean hyperglycemic hormone (CHH) from Carcinus maenas, a 72 amino acid neuropeptide, originates in neurosecretory perikarya in the eyestalk ganglia. Poly (A)RNA was isolated from these perikarya and a cDNA library was prepared. Screening of 20,000 clones with a 26-mer oligonucleotide, corresponding to a partial sequence of CHH, yielded one positive clone with an insert of approximately 2,000 bp, which contained the complete coding sequence for a pre-pro CHH. This precursor consists of a putative 26 amino acid signal sequence, a 38 amino acid peptide of unknown function (Peptide C), and the CHH sequence at the carboxyl end. The CHH-sequence is flanked N-terminally by a Lys-Arg cleavage site and C-terminally by the tetrapeptide Gly-Arg-Lys-Lys which is followed by the stop codon.

Amino Acid Sequence↗
PubMedDate not supplied

Molecular pathophysiology and clinical manifestations of gonadotropin receptor defects.

The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) bind specific receptors, members of the G protein-coupled receptor superfamily. Mutations of gonadotropin receptors are classified into activating (constitutively active or gain-of-function mutations) and inactivating (loss-of-function mutations). Activating mutations of the LH receptor have been described in familial and sporadic forms of male-limited pseudoprecocious puberty, whereas they do not appear to have any particular phenotype in females. The only activating mutation of the FSH receptor described to date was found in a hypophysectomized man who was fertile despite undetectable serum gonadotropin levels; the effects of constitutive FSH receptor activity in the context of normal pituitary function are not known. Homozygous inactivating mutations of the LH and FSH receptor invariably lead to amenorrhea in genotypical female subjects. In males, inactivation of the LH receptor in its more severe form results in a clinical picture similar to the syndrome of complete androgen resistance, but milder forms of hypoandrogenization have been described as well. In males, homozygous inactivation of the FSH receptor can also be associated with infertility. Finally, polymorphic variants of the FSH receptor are present in the normal population.

Animals↗
PubMedDate not supplied

Constitutively active mutations of G protein-coupled receptors: the case of the human luteinizing hormone and follicle-stimulating hormone receptors.

Activating mutations of the luteinizing hormone receptor (LHR) and the follicle-stimulating hormone receptor (FSHR) have been known for several years. These activating mutations permanently stimulate, in the absence of their cognate ligand, the receptor signaling pathways. In the case of the LHR, the induced chronic stimulation causes sporadic and familial pseudoprecocious puberty, a phenotype observed only in males. The absence of a female phenotype is probably due to the requirement for FSH in the induction of LHR expression. For the FSHR, one activating mutation was found in a patient with normal spermatogenesis without detectable gonadotropins. Whether activating mutations of the gonadotropin receptors are involved in tumor development is not yet clear. Activating mutations of the FSHR were supposedly involved but not found in ovarian tumors. For the LHR, only one patient with a seminoma and an activating mutation was described. The different occurrence of activating mutations of the LHR compared to the FSHR is surprising, since the two genes are adjacently located on chromosome 2 and should therefore be affected by a similar mutation rate. It might well be that mutations occur with the same frequency, but that activating mutations of the FSHR do not result in any particular phenotype.

Animals↗
PubMedDate not supplied

Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction.

The FSH receptor shows three single nucleotide polymorphisms (SNPs), one in the promoter and two in exon 10. In addition, the FSH receptor mRNA undergoes extensive alternative splicing. While no physiological role for the SNP in the promoter and for alternative spliced isoforms has been demonstrated so far, the SNPs in exon 10 result in four discrete allelic variants characterized by the amino acid combinations Thr307-Asn680, Ala307-Ser680, Ala307-Asn680 and Thr307-Ser680. Several studies have demonstrated that the first two allelic variants are very frequent (approximately 60 and 40% respectively) in the Caucasian population. The rarer Ala307-Asn680 and Thr307-Ser680 variants are much less frequent (<5%) in the Chinese. In males the FSH receptor variants are not related to testicular volume, serum FSH or serum inhibin B levels. The two most common receptor variants transiently transfected in COS-7 cells displayed similar functional characteristics. Frequency distribution of the two polymorphisms in normal women and patients with polycystic ovarian syndrome or premature ovarian failure is still under investigation. The homozygous Ala307-Ser680 variant seems to be associated with significantly higher basal serum FSH levels and with a higher amount of FSH required for ovarian stimulation in women undergoing assisted reproduction. This suggests that the FSH receptor genotype can influence the ovarian response to FSH stimulation. The presence of SNPs in the FSH receptor gene capable of modifying FSH action paves the way for future patient-tailored, genotype-based hormone therapies.

Alleles↗