Expression and Function of Somatostatin Receptor Subtype 1 in Human Growth Hormone Secreting Pituitary Tumors Deriving from Patients Partially Responsive or Resistant to Long-Term Treatment with Somatostatin Analogs

2004 ◽  
Vol 79 (3) ◽  
pp. 142-148 ◽  
Author(s):  
C. Matrone ◽  
R. Pivonello ◽  
A. Colao ◽  
P. Cappabianca ◽  
L.M. Cavallo ◽  
...  
2016 ◽  
Vol 174 (5) ◽  
pp. 651-662 ◽  
Author(s):  
Federico Gatto ◽  
Nienke R Biermasz ◽  
Richard A Feelders ◽  
Johan M Kros ◽  
Fadime Dogan ◽  
...  

AbstractObjectiveThe high expression of somatostatin receptor subtype 2 (SSTR2 also known as sst2) usually present in growth hormone (GH)-secreting adenomas is the rationale for therapy with somatostatin analogs (SSAs) in acromegaly. Although SSTR2 expression is a good predictor for biochemical response to SSA treatment, we still face tumors resistant to SSAs despite high SSTR2 expression. Recently, beta-arrestins (β-arrestins) have been highlighted as key players in the regulation of SSTR2 function.DesignTo investigate whether β-arrestins might be useful predictors of responsiveness to long-term SSA treatment in acromegaly, we retrospectively evaluated 35 patients with acromegaly who underwent adenomectomy in two referral centers in The Netherlands.Methodsβ-arrestin mRNA levels were evaluated in adenoma samples, together with SSTR2 (and SSTR5) mRNA and protein expression. Biochemical response to long-term SSA treatment (median 12 months) was assessed in 32 patients.Resultsβ-arrestin 1 and 2 mRNA was significantly lower in adenoma tissues from patients who achieved insulin-like growth factor 1 normalization (P= 0.024 andP= 0.047) and complete biochemical control (P= 0.047 andP= 0.039). The SSTR2 mRNA was higher in SSA responder patients compared with the resistant ones (P= 0.026). This difference was more evident when analyzing the SSTR2/β-arrestin 1 and SSTR2/β-arrestin 2 ratio (P= 0.011 andP= 0.010). β-arrestin 1 and 2 expression showed a significant trend of higher median values from full responders, partial responders to resistant patients (P= 0.045 andP= 0.021, respectively). Interestingly, SSTR2 protein expression showed a strong inverse correlation with both β-arrestin 1 and 2 mRNA (ρ= –0.69,P= 0.0011 andρ= –0.67,P= 0.0016).ConclusionsLow β-arrestin expression and high SSTR2/β-arrestin ratio correlate with the responsiveness to long-term treatment with SSAs in patients with acromegaly.


1979 ◽  
Vol 48 (3) ◽  
pp. 472-477 ◽  
Author(s):  
DANIEL RUDMAN ◽  
MICHAEL H. KUTNER ◽  
MARTIN A. GOLDSMITH ◽  
R.DWAIN BLACKSTON

Metabolism ◽  
1964 ◽  
Vol 13 (2) ◽  
pp. 152-160 ◽  
Author(s):  
Herbert Gershberg ◽  
Silvia Mari ◽  
Mildred Hulse ◽  
Henry St. Paul

1972 ◽  
Vol 69 (3) ◽  
pp. 417-433 ◽  
Author(s):  
Kerstin Hall ◽  
Patrick Olin

ABSTRACT Twenty patients with pituitary dwarfism were treated for nine months to 2½ years with human growth hormone (HGH) prepared according to Roos et al. (1963). Eleven of them had previously been given other HGH preparations for one to five years. During the first two years of treatment with HGH in a dose of 0.2 mg (0.4 IU) and 0.3 mg (0.6 IU) per kg body weight per week, the increase in growth rate was two- to threefold, and three- to fivefold, respectively. Long-termed treatment with HGH was accompanied by a decreasing ability of the hormone to stimulate growth. Cortisone acetate, in replacement doses, had no influence on this growth rate. During the present study only one of the 20 patients developed antibodies to HGH. The levels of sulphation factor (SF) activity in serum were low before treatment and increased significantly during treatment with HGH. There was a linear relationship between the SF activity in the serum and the slope of the growth carves. Both increased with the dose of HGH administered but decreased with duration of treatment.


1991 ◽  
Vol 130 (3) ◽  
pp. 435-441 ◽  
Author(s):  
M. E. Wilson ◽  
J. M. Tanner

ABSTRACT Female rhesus monkeys (n = 5), having normal pituitary function, were treated for 50 months with recombinant human growth hormone (rhGH; 250 μg/kg) 3 days/week (Monday, Wednesday and Friday) and rates of growth were compared with a group of age-matched untreated females (n = 6). Treatment was initiated at 20 months of age, approximately 10 months before the expected age of menarche. Long-term treatment with rhGH accelerated bone maturation and increased the velocity of increase in crown–rump length, tibia length and body weight. The period of acceleration occurred coincident with the occurrence of spontaneous puberty. Body measurements remained larger in the treated females until growth ceased. Long-term rhGH treatment increased final adult crown–rump length by some 3%, with a slight increase in tibia length and body weight, without having any untoward effects on reproductive capacity or health. One treated animal exhibited higher estimates of antibodies to rhGH throughout the study period, and this female also had a smaller increment in crown–rump length than the other treated females. These data suggest that long-term treatment of normal-pituitary females with rhGH augments crown–rump growth without any untoward effects of health. Journal of Endocrinology (1991) 130, 435–441


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