scholarly journals Development of A Recombinant Murine Luteinizing Hormone Binding Protein As A Selective Hormone Inhibitor

2021 ◽  
Author(s):  
Yusuke Yamaguchi ◽  
Yorino Sato ◽  
Kazuhiro Kawamura
Keyword(s):  
Luteinizing Hormone ◽  
Binding Protein ◽  
Follicular Development ◽  
Mouse Serum ◽  
Camp Production ◽  
Cleavage Reaction ◽  
Ovarian Dysfunction ◽  
Binding Ability ◽  
293 Cells ◽  
Hormone Binding Protein

Abstract Physiological levels of luteinizing hormone (LH), in concert with follicle stimulating hormone (FSH), promote ovarian follicular development and ovulation. However, high LH levels associated with ovarian dysfunction have been shown to inhibit these processes. Thus, developing a selective LH inhibitor could be potentially useful for treating ovarian dysfunction. Here, we developed a mouse LH-binding protein (mLBP) composed of the extracellular domain of LH receptors as a selective inhibitor of mouse LH. After transient introduction of mLBP expressing vectors into Expi293F cells, mLBP was obtained as a soluble protein via a cleavage reaction with thrombin. The binding ability of mLBP for mouse LH was confirmed using sera containing high LH and FSH collected from ovariectomized (OVX) mice. The bioactivity of mLBP was demonstrated by inhibition of cAMP and testosterone productions induced by OVXmouse serum in mouse Leydig MLTC-1 cells expressing LH receptors. In contrast, mLBP did not bind mouse FSH and inhibit cAMP production induced by OVX-mouse serum in 293 cells expressing mouse FSH receptors. The mLBP also showed binding affinity to human LH (hLH), and inhibited hLH-induced cAMP production in MLTC-1 cells. Thus, the mLBP selectively suppresses the action of LH and is a potential therapeutic agent for ovarian dysfunction.

Concentration of free growth hormone-binding protein in the serum of mice is not regulated by growth hormone

1997 ◽  
Vol 153 (2) ◽  
pp. 319-325 ◽  
Author(s):  
A I Sotelo ◽  
F P Dominici ◽  
A Bartke ◽  
D Turyn
Keyword(s):  
Growth Hormone ◽  
Binding Protein ◽  
High Capacity ◽  
Peripheral Circulation ◽  
Mouse Serum ◽  
High Affinity ◽  
Ames Dwarf Mice ◽  
Ames Dwarf ◽  
Hormone Binding Protein ◽  
Dwarf Mice

Abstract Ames dwarf mice that do not express growth hormone (GH) or prolactin (PRL) genes were used to study the effects of GH deficiency on the presence and the characteristics of GH-binding protein (GHBP) in serum. Chromatographic techniques were used to allow characterization of biological rather than immunological activity of GHBP. Two GH-binding fractions were found in dwarf mice serum, one with low affinity and high capacity (GHBPI) and one with high affinity, low capacity and lower molecular mass (GHBPII). Serum concentration of the high-affinity GHBP was 0·73 ± 0·03 nm with a Kd of 6·3 ± 1·7 nm. Since Ames dwarf mice have no GH in the circulation, all the GHBP is free. Interestingly, the concentration of GHBP in dwarf mice was similar to the levels of free GHBP measured in normal mice from the same line. Moreover, this value (0·7 nm) closely resembles the concentration of free GHBP in the serum of transgenic mice overexpressing GH, in which peripheral GH levels are grossly elevated. These observations can be interpreted as evidence that the levels of free GHBP in mouse serum are independent of GH concentration, and that GH influences only the levels of bound GHBP in peripheral circulation. Journal of Endocrinology (1997) 153, 319–325

P–678 Increased luteinizing hormone in ovarian dysfunction attenuates follicle development and oocyte quality in human

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Tanaka ◽  
K Kawamura
Keyword(s):  
Luteinizing Hormone ◽  
Ovarian Stimulation ◽  
Follicular Development ◽  
Oocyte Quality ◽  
Follicle Development ◽  
Follicle Growth ◽  
Ovarian Dysfunction ◽  
High Quality ◽  
Group A ◽  
Group B

Abstract Study question Can increased luteinizing hormone impair follicular development and oocyte quality in patients with ovarian dysfunction? Summary answer Increased luteinizing hormone attenuates follicular development and oocyte quality, resulting in arrest of follicle growth and empty follicles and low-quality embryos. What is known already Patients with ovarian dysfunction exhibit elevated gonadotropins and low estrogen levels reflecting their low ovarian reserve. For ovarian stimulation in these patients, natural or mild stimulation protocols are likely used, but we often experienced the arrest of follicle growth and empty follicles at oocyte retrieval. Animal studies demonstrated that chronic high LH exposure impaired the growth of antral follicles by suppressing the expression of FSHR in granulosa cells via a modulation of intraovarian regulators, including the LH-induced thecal factors. Study design, size, duration: Retrospective analysis was conducted in 72 patients with ovarian dysfunction who received ovarian stimulations followed by IVF-ET from April 2018 to March 2020 after obtaining written informed consents under an approval from the ethical committee of our hospital. Participants/materials, setting, methods The data of hormonal levels, transvaginal ultrasound during ovarian stimulation and clinical outcome of IVF were extracted from electric chart. For evaluation of embryo, high quality embryos referred to embryos having Veeck classification >grade 3 and >4 blastomeres. Statistical significance was determined using Dunnett or chi-square tests, with P < 0.05 being statistically significant. Main results and the role of chance The median age of participants was 42 years of age (range 26–49) with low serum AMH levels (median 0.9 ng/ml, range 0–1.83). We analyzed 361 cycles of ovarian stimulation in total (median 4 cycles/patient, range 1–21). These stimulation cycles were classified into 3 groups; group A (n = 230): normal LH level, group B (n = 93): elevated LH level (> 10 mIU/ml) after ovarian stimulation and group C (n = 33): elevated LH level from the initiation of ovarian stimulation. Among 361 cycles, the arrest of follicle growth was detected in 5 cycles (group A: 0%, group B: 60%, group C: 40%). The proportions of empty follicle in group A, B and C were 17.3±2.0%, 20.9±3.3%and 38.6±7.2%, respectively. The rate of empty follicle was significantly high in group C. Although there was no significant difference in the rates of oocyte degeneration and fertilization, the rate of high-quality embryos in group C was 0.8-fold lower than that of group A. Limitations, reasons for caution Due to limitation of participants, we could not determine the appropriate LH level for ovarian stimulation in patients with ovarian dysfunction based on receiver operatorating characteristic curve. Wider implications of the findings: Normalization of LH levels for ovarian simulation in patients with ovarian dysfunction could improve follicle development and oocyte quality. Trial registration number Not applicable

scholarly journals Purification, Molecular Cloning, and Functional Expression of the Human Nicodinamide-Adenine Dinucleotide Phosphate-Regulated Thyroid Hormone-Binding Protein

1997 ◽  
Vol 11 (11) ◽  
pp. 1728-1736 ◽  
Author(s):  
Marie-Pierre Vié ◽  
Claudine Evrard ◽  
Jeannine Osty ◽  
Aline Breton-Gilet ◽  
Pascal Blanchet ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Molecular Cloning ◽  
Binding Protein ◽  
Functional Expression ◽  
Hormone Binding ◽  
Hormone Binding Protein

Growth hormone-binding protein levels: Studies of children with short stature

Metabolism ◽  
1994 ◽  
Vol 43 (3) ◽  
pp. 357-359 ◽  
Author(s):  
Nelly Mauras ◽  
Lena M.S. Carlsson ◽  
Suzanne Murphy ◽  
Thomas J. Merimee
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Binding Protein ◽  
Hormone Binding ◽  
Protein Levels ◽  
Growth Hormone Binding Protein ◽  
Hormone Binding Protein
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