Expression of Luteinizing Hormone Receptor in the Gastrointestinal Tract in Patients with and without Dysmotility

Hammar, Oskar; Veress, B; Montgomery, Agneta; Ohlsson, Bodil

doi:10.4137/dti.s9324

Cited by 17 publications

(25 citation statements)

References 27 publications

(44 reference statements)

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“…LH-R has been demonstrated in submucous and myenteric neurons in small and large intestine, glia cells and endothelial cells in man [17], while in rat LH-R-IR was exclusively confined to enteric neurons [15]. In the former publication, no absorption controls were performed in man, but our present findings confirm LH-R on submucous and myenteric neurons.…”

Section: Discussionsupporting

confidence: 72%

“…Our present and previous findings of GnRH and LH-R in human and LH-R in rat gastrointestinal tract [12,15,17,18], may provide an explanation for the small intestinal dysmotility noted after administration of GnRH analogs or LH [9,10,11]. Patients with enteric dysmotility and chronic intestinal pseudo-obstruction exhibit disturbances in small intestinal motility patterns [26,27].…”

Section: Discussionmentioning

confidence: 96%

“…Paraffin sections of ileum from one man (20 years of age) diagnosed with enteric inflammatory neuropathy [12,17] and from one woman (30 years of age) diagnosed with enteric degenerative neuropathy [12,18] were used for immunocytochemistry. In addition, ileum tissue was collected from one woman (84 years of age) undergoing gastrointestinal surgery due to sigmoideum diverticulosis, and colonic tissue from one woman (65 years of age) with non-obliterating adenocarcinoma of rectosigmoideum and one woman (68 years of age) due to sigmoideum diverticulosis.…”

Section: Manmentioning

confidence: 99%

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Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Sand

Bergvall

Ekblad

et al. 2013

Regulatory Peptides

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 96%

Section: Manmentioning

confidence: 99%

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Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Sand

Bergvall

Ekblad

et al. 2013

Regulatory Peptides

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“…In contrast, other groups have observed GnRH and GnRH receptor immunoreactivity in rat enteric neurons, smooth muscle cells, and epithelial parietal cells [11,12,13,14], and still more have found GnRH receptor mRNA in enteric neurons [15]. LH receptors have been described on enteric neurons in both rats and humans [7,10,16,17] (table 1). The LH receptor belongs to the rhodopsin/β 2 -adrenergic receptor-like family A of the G-protein-coupled receptor group and is predominantly expressed in the gonads [18].…”

Section: Expression Of Gnrh and Gonadotropins In The Gastrointestinalmentioning

confidence: 98%

“…GnRH analogs stimulate the anterior pituitary, resulting in elevated LH secretion along with the stimulation of LH receptors and elevated steroidal sex hormone secretion [1,2,3,50]. The harmful effects evoked in the gastrointestinal tract could be mediated by this route because LH receptors are found in the gastrointestinal tract in humans and rats [7,10,16,17], and they are downregulated following GnRH stimulation [10]. Elevated serum levels of estradiol following buserelin treatment along with the secondary synchronization of hormonal cycles and a thickened uterine muscle layer [50] confirm the presence of elevated FSH and LH secretion in a rat model [10].…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-Releasing Hormone and Its Physiological and Pathophysiological Roles in Relation to the Structure and Function of the Gastrointestinal Tract

Ohlsson

2016

Eur Surg Res

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Background: Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are involved in the reproductive cycle and regulate the secretion of sex steroids from the gonads. In mammals, GnRH1 is secreted as a hormone from the hypothalamus, whereas both GnRH1 and GnRH2 are present as neuropeptides in a variety of tissues. This review describes the role of GnRH in the gastrointestinal tract. Summary: GnRH1, GnRH2, and LH receptors in humans and rats, and GnRH receptors in rats, have been described in the gastrointestinal tract, where they affect motility, gastric and hormone secretion, and cell proliferation. GnRH analogs are clinically used in the treatment of sex hormone-dependent diseases, i.e., endometriosis and malignancies, and as pretreatments for in vitro fertilization. Severe gastrointestinal dysmotility has been shown to develop in some women after such treatment, along with a reduction in the number of enteric neurons and autoantibodies against GnRH. Consequently, a rat model of enteric neurodegeneration has been developed based on the administration of the GnRH analog buserelin. Serum IgM antibodies against GnRH1, the GnRH2 precursor progonadoliberin-2, and the GnRH receptor have also been described in patients with irritable bowel syndrome and dysmotility, as well as in patients with gastrointestinal disorders associated with diabetes mellitus, posterior laryngitis, and primary Sjögren's syndrome, although no treatments using GnRH analogs have been administered. Conclusion: GnRH and receptors for GnRH and LH are present in the human and rat gastrointestinal tract. Treatment with GnRH analogs may induce severe dysmotility, and a rat model of enteric neurodegeneration has been developed based on stimulation by the GnRH analog buserelin. Autoantibodies against GnRH and its receptor are found in a subgroup of patients with functional bowel disorders and dysmotility, independent of treatment with GnRH analogs.

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Gonadotropin-releasing hormone analog buserelin causes neuronal loss in rat gastrointestinal tract

et al. 2012

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Gonadotropin-releasing hormone (GnRH) analogs are given to women undergoing in vitro fertilization. Case reports describing the development of chronic intestinal pseudo-obstruction and auto-antibodies against GnRH after such treatment suggest a strong association between intestinal dysfunction and GnRH analogs. No experimental model for studying such a relationship is currently at hand. Our main goal was to investigate possible enteric neurodegeneration and titers of GnRH antibodies in response to repeated administration of the GnRH analog buserelin in rat. Rats were treated for 1-4 sessions with daily subcutaneous injections of buserelin or saline for 5 days, followed by 3 weeks of recovery. Buserelin treatment caused significant loss of submucous and myenteric neurons in the fundus, ileum, and colon. The loss of enteric neurons can, at least partly, be explained by increased apoptosis. No GnRH- or GnRH-receptor-immunoreactive (IR) enteric neurons but numerous luteinizing hormone (LH)-receptor-IR neurons were detected. After buserelin treatment, the relative number of enteric LH-receptor-IR neurons decreased, whereas that of nitric-oxide-synthase-IR neurons increased. No intestinal inflammation or increased levels of circulating interleukins/cytokines were noted in response to buserelin treatment. Serum GnRH antibody titers were undetectable or extremely low in all rats. Thus, repeated administrations of buserelin induce neurodegeneration in rat gastrointestinal tract, possibly by way of LH-receptor hyperactivation. The present findings suggest that enteric neurodegenerative effects of GnRH analog treatment in man can be mimicked in rat. However, in contrast to man, no production of GnRH auto-antibodies has been noted in rat.

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Expression of Luteinizing Hormone Receptor in the Gastrointestinal Tract in Patients with and without Dysmotility

Cited by 17 publications

References 27 publications

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Gonadotropin-Releasing Hormone and Its Physiological and Pathophysiological Roles in Relation to the Structure and Function of the Gastrointestinal Tract

Gonadotropin-releasing hormone analog buserelin causes neuronal loss in rat gastrointestinal tract

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