Growth Hormone increases gonadotropin receptors in poor-prognosis patients

Introduction: Growth hormone (GH) exerts multiple functions including its effect on the reproductive system1. We have recently reported that GH supplementation improves implantation and pregnancy rates for poor-prognosis patients undertaking stimulated IVF2. The purpose of this study was to understa...

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Main Authors: Regan, S., Stanger, J., Yovich, J., Almahbobi, Ghanim
Other Authors: Oxford Journals
Format: Conference Paper
Published: Oxford University press 2012
Online Access:http://hdl.handle.net/20.500.11937/11118
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author Regan, S.
Stanger, J.
Yovich, J.
Almahbobi, Ghanim
author2 Oxford Journals
author_facet Oxford Journals
Regan, S.
Stanger, J.
Yovich, J.
Almahbobi, Ghanim
author_sort Regan, S.
building Curtin Institutional Repository
collection Online Access
description Introduction: Growth hormone (GH) exerts multiple functions including its effect on the reproductive system1. We have recently reported that GH supplementation improves implantation and pregnancy rates for poor-prognosis patients undertaking stimulated IVF2. The purpose of this study was to understand the underlying mechanism of action of GH on developing human follicles and possibly oocytes, leading to such improvement. Material and Methods: Granulosa cells were collected at trans-vaginal oocyte recovery from 137 age-matched gonadotrophin-stimulated patients with or without GH supplementation. Such patients were those achieving few mature oocytes despite high dose gonadotrophin stimulation. Their cells were purified, immuno-labelled with fluorescent antibodies and analyzed by flow cytometry to quantify receptors (R) of GH, FSH, LH and Bone Morphogenetic Proteins (BMPs).Results: The levels of GHR on granulosa cells were significantly elevated (p < 0.003) in patients treated with exogenous GH, suggesting an auto-upregulation mechanism. In addition, GHR was significantly increased (p < 0.02) in cells from older (>35y, n = 69) patients than from younger (<35y, n = 54). Of further interest, the expression of FSHR and LHR was significantly increased (p < 0.001 and p < 0.05, respectively) on granulosa cells from treated patients (n = 36) compared with age-matched (39-45y) untreated patients (n = 40). On the other hand, the levels of BMPR which correlates with early apoptosis were also significantly increased (p < 0.0005 and p < 0.005, respectively) in cells from treated patients (n = 36) compared with untreated (n = 40). Conclusions: We conclude that treatment of poor-responder patients using exogenous GH leads to an increase in the levels of FSHR and LHR on granulosa cells hence increasing the sensitivity of follicles to gonadotrophin stimulation. Enhanced response to gonadotrophins may explain the beneficial clinical response previously reported by us. There may also be indirect effects operating that improve the developmental potential of the oocytes. Regardless of the mechanism, this outcome endorses the simple clinical practice of GH supplementation to improve the fertility rates of poor-prognosis patients, particularly those in the older reproductive age range.
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spelling curtin-20.500.11937-111182017-01-30T11:22:57Z Growth Hormone increases gonadotropin receptors in poor-prognosis patients Regan, S. Stanger, J. Yovich, J. Almahbobi, Ghanim Oxford Journals Introduction: Growth hormone (GH) exerts multiple functions including its effect on the reproductive system1. We have recently reported that GH supplementation improves implantation and pregnancy rates for poor-prognosis patients undertaking stimulated IVF2. The purpose of this study was to understand the underlying mechanism of action of GH on developing human follicles and possibly oocytes, leading to such improvement. Material and Methods: Granulosa cells were collected at trans-vaginal oocyte recovery from 137 age-matched gonadotrophin-stimulated patients with or without GH supplementation. Such patients were those achieving few mature oocytes despite high dose gonadotrophin stimulation. Their cells were purified, immuno-labelled with fluorescent antibodies and analyzed by flow cytometry to quantify receptors (R) of GH, FSH, LH and Bone Morphogenetic Proteins (BMPs).Results: The levels of GHR on granulosa cells were significantly elevated (p < 0.003) in patients treated with exogenous GH, suggesting an auto-upregulation mechanism. In addition, GHR was significantly increased (p < 0.02) in cells from older (>35y, n = 69) patients than from younger (<35y, n = 54). Of further interest, the expression of FSHR and LHR was significantly increased (p < 0.001 and p < 0.05, respectively) on granulosa cells from treated patients (n = 36) compared with age-matched (39-45y) untreated patients (n = 40). On the other hand, the levels of BMPR which correlates with early apoptosis were also significantly increased (p < 0.0005 and p < 0.005, respectively) in cells from treated patients (n = 36) compared with untreated (n = 40). Conclusions: We conclude that treatment of poor-responder patients using exogenous GH leads to an increase in the levels of FSHR and LHR on granulosa cells hence increasing the sensitivity of follicles to gonadotrophin stimulation. Enhanced response to gonadotrophins may explain the beneficial clinical response previously reported by us. There may also be indirect effects operating that improve the developmental potential of the oocytes. Regardless of the mechanism, this outcome endorses the simple clinical practice of GH supplementation to improve the fertility rates of poor-prognosis patients, particularly those in the older reproductive age range. 2012 Conference Paper http://hdl.handle.net/20.500.11937/11118 Oxford University press restricted
spellingShingle Regan, S.
Stanger, J.
Yovich, J.
Almahbobi, Ghanim
Growth Hormone increases gonadotropin receptors in poor-prognosis patients
title Growth Hormone increases gonadotropin receptors in poor-prognosis patients
title_full Growth Hormone increases gonadotropin receptors in poor-prognosis patients
title_fullStr Growth Hormone increases gonadotropin receptors in poor-prognosis patients
title_full_unstemmed Growth Hormone increases gonadotropin receptors in poor-prognosis patients
title_short Growth Hormone increases gonadotropin receptors in poor-prognosis patients
title_sort growth hormone increases gonadotropin receptors in poor-prognosis patients
url http://hdl.handle.net/20.500.11937/11118