Isolation and properties of the FSH and LH-releasing hormone

Schally, Andrew V.; Arimura, Akira; Baba, Yoshihiko; Nair, R. M. G.; Matsuo, Hisayuki; Redding, Tommie W.; Debéljuk, Luciano; White, W. F.

doi:10.1016/0006-291x(71)90766-2

Cited by 639 publications

(213 citation statements)

References 9 publications

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“…The quest to determine the structure of these releasing factors was spearheaded by the groups of McCann, Schally and Guillemin. In 1971, after a monumental purification effort from millions of pig brains, Schallyfirst announced the structure of the decapeptide GnRH [5,80,125] (Fig. 3).…”

Section: Introductionmentioning

confidence: 99%

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

Millar

Pawson

Morgan

et al. 2008

Frontiers in Neuroendocrinology

123

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Geoffrey Wingfield Harris' demonstration of hypothalamic hormones regulating pituitary function led to their structural identification and therapeutic utilization in a wide spectrum of diseases. Amongst these, Gonadotropin Releasing Hormone (GnRH) and its analogs are widely employed in modulating gonadotropin and sex steroid secretion to treat infertility, precocious puberty and many hormone-dependent diseases including endometriosis, uterine fibroids and prostatic cancer. While these effects are all mediated via modulation of the pituitary gonadotrope GnRH receptor and the G q signaling pathway, it has become increasingly apparent that GnRH regulates many extrapituitary cells in the nervous system and periphery. This review focuses on two such examples, namely GnRH analog effects on reproductive behaviors and GnRH analog effects on the inhibition of cancer cell growth. For both effects the relative activities of a range of GnRH analogs is distinctly different from their effects on the pituitary gonadotrope and different signaling pathways are utilized. As there is only a single functional GnRH receptor type in man we have proposed that the GnRH receptor can assume different conformations which have different selectivity for GnRH analogs and intracellular signaling proteins complexes. This ligand-induced selective-signaling recruits certain pathways while by-passing others and has implications in developing more selective GnRH analogs for highly specific therapeutic intervention.

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Section: Introductionmentioning

confidence: 99%

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

Millar

Pawson

Morgan

et al. 2008

Frontiers in Neuroendocrinology

123

View full text Add to dashboard Cite

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“…Subsequent studies led to the hypothesis that the pituitary is controlled by a hypothalamic factor (3)(4)(5)(6). It was not until 1971, however, that the amino acid sequence of GnRH was determined after extraction from the hypothalami of thousands of pigs and sheep by the groups of Schally and Guillemin (7,8).…”

mentioning

confidence: 99%

GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism

Chan

Guillebon

Lang‐Muritano

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

181

138

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Idiopathic hypogonadotropic hypogonadism (IHH) is a condition characterized by failure to undergo puberty in the setting of low sex steroids and low gonadotropins. IHH is due to abnormal secretion or action of the master reproductive hormone gonadotropin-releasing hormone (GnRH). Several genes have been found to be mutated in patients with IHH, yet to date no mutations have been identified in the most obvious candidate gene, GNRH1 itself, which encodes the preprohormone that is ultimately processed to produce GnRH. We screened DNA from 310 patients with normosmic IHH (nIHH) and 192 healthy control subjects for sequence changes in GNRH1. In 1 patient with severe congenital nIHH (with micropenis, bilateral cryptorchidism, and absent puberty), a homozygous frameshift mutation that is predicted to disrupt the 3 C-terminal amino acids of the GnRH decapeptide and to produce a premature stop codon was identified. Heterozygous variants not seen in controls were identified in 4 patients with nIHH: 1 nonsynonymous missense mutation in the eighth amino acid of the GnRH decapeptide, 1 nonsense mutation that causes premature termination within the GnRH-associated peptide (GAP), which lies C-terminal to the GnRH decapeptide within the GnRH precursor, and 2 sequence variants that cause nonsynonymous amino-acid substitutions in the signal peptide and in GnRH-associated peptide. Our results establish mutations in GNRH1 as a genetic cause of nIHH.GnRH ͉ luteinizing hormone-releasing hormone ͉ LHRH

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“…[25] GnRH is considered as an indirect means of androgenic enhancement due to LH increase which offers stimulation of the Leydig cells of the testis leading to an increase of blood testosterone concentrations in human males. [26] The use of aptamers as an alternative to antibodies in the enrichment of peptide targets from equine urine has been proposed in the study of Richards et al [27] using GnRH as a model compound.…”

Section: Gonadotropin-releasing Hormonementioning

confidence: 99%

Challenges in detecting substances for equine anti‐doping

Fragkaki

Kioukia‐Fougia

Kiousi

et al. 2017

Drug Testing and Analysis

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The artificial increase of the physical capability of horses using drugs is well known in racing and other equine sports. Both illicit and therapeutic substances are regarded as prohibited substances in competition in most countries. Some countries make distinctions for a few, specific drugs which are, however, allowed for use in other countries. The primary objective in the case of doping control is the detection of any trace of drug exposure, either parent drug or any of its metabolites, using the most powerful analytical methods which are generally based on chromatographic/mass spectrometric techniques. Of major concern in horseracing is the absence of a single organization regulating the anti-doping framework; instead of this, individual racing authorities provide rules and regulations often resulting in variations in the applied doping control programmes of different countries. The aim of this paper is to review the recent literature (approximately from 2012 to mid-2016) to highlight the numerous and diverse challenges faced in doping control of racing and equestrian sports, including the detection of designer drugs (anabolic steroids or stimulants) and of other emerging prohibited substances, such as peptides and noble gases in horse urine and plasma. Moreover, the application of 'omics' techniques (especially of metabolomics) deserves attention for establishing possible fingerprints of drug abuse as well as the evolution of instrumental analysis resulting a powerful ally in the fight against doping in equine sports.

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Isolation and properties of the FSH and LH-releasing hormone

Cited by 639 publications

References 9 publications

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism

Challenges in detecting substances for equine anti‐doping

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