Glycoprotein hormone alpha-subunit production and plurihormonality in human corticotroph tumours—an in vitro and immunohistochemical study

1995 ◽  
Vol 133 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Bhaloo Desai ◽  
Jacqueline M Burrin ◽  
Catherine A Nott ◽  
Jennian F Geddes ◽  
Edmund J Lamb ◽  
...  

Desai B, Burrin JM, Nott CA, Geddes JF, Lamb EJ, Aylwin SJB, Wood DF, Thakkar C, Monson JP. Glycoprotein hormone alpha-subunit production and plurihormonality in human corticotroph tumours—an in vitro and immunohistochemical study. Eur J Endocrinol 1995;133:25–32. ISSN 0804–4643 Glycoprotein hormone alpha-subunit (αSU) is a recognized product of clinically non-functioning, glycoprotein hormone-secreting and somatotroph adenomas but has not been studied systematically in corticotroph tumours. We have performed immunohistochemistry for αSU in a consecutive series of four corticotroph tumours causing Nelson's syndrome, three corticotroph macroadenomas, 12 corticotroph microadenomas and one adrenocorticotrophin-secreting bronchial carcinoid tumour. In addition we have assessed αSU secretion in vitro in corticotroph adenomas from two subjects with Cushing's disease and two subjects with Nelson's syndrome. Immunohistochemistry, performed after microwave treatment of sections to enhance antigen retrieval, demonstrated αSU positivity in 3/4 Nelson's tumours, 2/3 corticotroph macroadenomas, 7/12 microadenomas and one bronchial carcinoid. Eight of the 13 tumours positive for αSU were also immunostained after microwave pretreatment of sections for thyrotrophin (six positive), follicle-stimulating hormone (four positive), luteinizing hormone (three positive), β-chorionic gonadotrophin (five positive), growth hormone (three positive) and prolactin (two positive) immunoreactivity. In vitro cell cultures of all four tumours studied secreted adrenocorticotrophin and three secreted αSU, with the variable presence of luteinizing hormone, follicle-stimulating hormone, thyrotrophin, growth hormone and prolactin, in basal culture. The αSU secretion was augmented by phorbol ester (160 ± 15%, sem, n = 3 wells; p < 0.01) and 8-bromo-cAMP (138 ± 8%; p < 0.05) in one tumour. These data indicate that plurihormonality and, in particular, αSU elaboration and secretion by corticotroph tumours is more common than hitherto recognized. Possible mechanisms include abnormal or deregulated gene expression, autocrine or paracrine effects or a stem cell origin of tumour. The possible relationship of αSU production to corticotroph tumour behaviour and prognosis remains to be established. John P Monson, Dept of Endocrinology, Royal London Hospital, Whitechapel, London El 1BB, UK

1968 ◽  
Vol 46 (4) ◽  
pp. 639-647
Author(s):  
J. K. Davidson ◽  
R. E. Haist

The effects of various levels of several substrates and hormones on the glycogen content of mouse hemidiaphragm in vitro in the presence and absence of insulin were determined. Pyruvate (0.64 mg/ml) increased glycogen. Acetoacetate (0.16 mg/ml), β-hydroxybutyrate (2.5 mg/ml), and lactate (2.5 mg/ml) increased glycogen only in the presence of glucose and insulin. A mixture of 19 amino acids (0.2 mg/ml of each) had no effect. Growth hormone (100 μg/ml) had no effect in the absence of insulin, but increased glycogen in the presence of glucose and insulin. Prolactin, thyrotrophin, luteinizing hormone, follicle-stimulating hormone, oxytocin, thyroxine, triiodothyronine, cysteine-treated glucagon, adrenocorticotrophic hormone (512 μg/ml), vasopressin (5.25 μg/ml), and Cortisol (16 μg/ml) had no effect. Epinephrine (0.01 μg/ml) and norepinephrine (0.1 μg/ml) had no effect, but epinephrine (0.1 μg/ml) and norepinephrine (1 μg/ml) decreased glycogen content. At physiologic levels of the tested materials, only glucose and insulin altered the glycogen content of mouse hemidiaphragm.


2004 ◽  
pp. 877-884 ◽  
Author(s):  
M Chopineau ◽  
N Martinat ◽  
JF Gibrat ◽  
C Galet ◽  
F Lecompte ◽  
...  

OBJECTIVE: To identify amino-acids in the alpha-subunit important for expression of heterospecific FSH activity of horse (e) LH/choriogonadotropin (CG) (eLH) and donkey (dk) LH/CG (dkLH) (FSH/LH ratio ten times higher for eLH than for dkLH); this FSH activity absolutely requires an equid (donkey or horse) alpha-subunit combined with an equid beta-LH subunit. DESIGN: Chimeric alpha-subunits possessing the first 63 amino-acids of the porcine (p) and the last 33 amino-acids of the donkey alpha-subunit (alphap-dk) and the inverse (alphadk-p) were constructed. Porcine-specific amino-acids were introduced by mutagenesis in donkey alpha-subunit at positions 70, 85, 89, 93 and 96 (alphadk5xmut), 18 (alphadkK18E) or 78 (alphadkI78A). METHODS: These different alpha-subunits were co-transfected in COS-7 cells with beta-eLH, beta-dkLH and beta-eFSH. The LH and FSH bioactivities of the dimers were then assessed in two heterologous in vitro bioassays. RESULTS: alphap-dk or alphadk-p exhibited FSH activity when co-expressed with beta-eLH but not with beta-dkLH. alphadkK18E or alphadkI78A gave hybrids with no FSH activity and important LH activity when expressed with beta-dkLH. alphadkI78A/betaeLH displayed an FSH/LH ratio as low as that of dkLH. However, mutation at 78 in alpha-dk had no effect on FSH bioactivity when co-expressed with beta-eFSH. CONCLUSIONS: Amino-acids present in both the first two-thirds and the last third of the alpha-subunit of equid LHs are involved in their heterologous biospecificity. Ile alpha78 exerts as strong an influence on it as the beta102-103 residues. By contrast, this residue plays no role in the FSH specificity of eFSH.


2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Dragos Albu ◽  
Alice Albu

Abstract We performed a retrospective study aiming to study the relationship between the ratio of the exogenous luteinizing hormone to follicle stimulating hormone (LH/FSH) administrated for controlled ovarian stimulation (COS) and the number and competence of the oocytes retrieved for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Eight hundred sixty-eight consecutive infertile patients (mean age 34.54 ± 4.01 years, mean anti-Müllerian hormone (AMH) 2.94 ± 2.07 ng/ml) treated with long agonist protocol and a mixed gonadotropin protocol (human menopausal gonadotropin in association with recombinant FSH (recFSH)) who performed IVF/ICSI between January 2013 and February 2016, were included. Patients with severe male factor were excluded. LH/FSH was calculated based on total doses of the two gonadotropins. We found, after adjustment for confounders, a positive relationship between LH/FSH and the retrieved oocytes’ (β = 0.229, P&lt;0.0001) and zygotes’ number (β = 0.144, P&lt;0.0001) in the entire study group and in subgroups according to age (&lt;35 and ≥35 years) and ovarian reserve (AMH &lt; 1.1 and ≥ 1.1 ng/ml). The fertilization rate was positively associated with LH/FSH in patients with LH/FSH in the lowest three quartiles (below 0.77) (β = 0.096, P=0.034). However, patients in the fourth quartile of LH/FSH had a lower fertilization rate as compared with patients in quartiles 1–3 which, after adjustment for covariates, was only marginally negatively related with LH/FSH (β = −0.108, P=0.05). In conclusion, our results suggest that the adequate LH/FSH administrated during COS can improve the oocytes’ and zygotes’ number in IVF/ICSI cycles, but also the fertilization rate when a certain proportion of LH/FSH is not exceeded.


2015 ◽  
Vol 25 (2) ◽  
pp. 85-89 ◽  
Author(s):  
M.K.B. Serafim ◽  
A.B.G. Duarte ◽  
G.M. Silva ◽  
C.E.A. Souza ◽  
D.M. Magalhães-Padilha ◽  
...  

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