Effects of GnRH Analogues on Growth and Bone Maturation: A Role for Growth Factors and Adrenal Androgens

Author(s):  
S. L. S. Drop ◽  
W. Oostdijk ◽  
A. J. H. Odink ◽  
C.-J. Partsch ◽  
R. Hummelink ◽  
...  
1999 ◽  
Vol 84 (2) ◽  
pp. 449-452 ◽  
Author(s):  
Anna Maria Pasquino ◽  
Ida Pucarelli ◽  
Maria Segni ◽  
Marco Matrunola ◽  
Fabio Cerrone

GnRH analogues (GnRHa) represent the treatment of choice in central precocious puberty (CPP), because arresting pubertal development and reducing either growth velocity (GV) or bone maturation (BA) should improve adult height. However, in some patients, GV decrease is so remarkable that it impairs predicted adult height (PAH); and therefore, the addition of GH is suggested. Out of twenty subjects with idiopathic CPP (treated with GnRHa depot-triptorelin, at a dose of 100 μg/kg im every 21 days, for at least 2–3 yr), whose GV fall below the 25th percentile for chronological age, 10 received, in addition to GnRHa, GH at a dose of 0.3 mg/kg·week sc, 6 days weekly, for 2–4 yr; and 10 matched for BA, chronological age, and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of GH addition. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean ± sem): 13.2 ± 0.2 in GnRHa plus GH vs. 13.0 ± 0.1 yr in the control group. At the conclusion of the study, all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than pretreatment PAH (160.6 ± 1.3 vs. 152.7 ± 1.7 cm). Target height (TH) was significantly exceeded. The group treated with GnRH alone reached an adult height not significantly higher than pretreatment PAH (157.1 ± 2.5 vs. 155.5 ± 1.9 cm). TH was just reached but not significantly exceeded. The gain in centimeters obtained, calculated between pretreatment PAH and final height, was 7.9 ± 1.1 cm in patients treated with GH combined with GnRHa; whereas in patients treated with GnRHa alone, the gain was just 1.6 ± 1.2 cm (P = 0.001). Furthermore, no side effects have been observed either on bone age progression or ovarian cyst appearance and the gynecological follow-up in the GH-treated patients (in comparison with those treated with GnRHa alone). In conclusion, a gain of 7.9 cm in adult height represents a significant improvement, which justifies the addition of GH for 2–3 yr during the conventional treatment with GnRHa, especially in patients with CPP, and a decrease in GV so marked as to impair PAH, not allowing it to reach even the third centile.


Earl puberty begins with activation of the gonadotrophic axis before 8 years of age in girls and at 9 years of age in boys. One of the main concerns is the height because it accelerates the bone maturation process resulting in reduced height. The standard treatment for precocious puberty is the use of deposits of GnRh analogues with the proposal to minimize the effects on growth. As a result, this literature review is based on demonstrating the effects of using GnRh analogues at the final height. Before and after 8 years of age.


Author(s):  
R. W. Tucker ◽  
N. S. More ◽  
S. Jayaraman

The mechanisms by which polypeptide growth factors Induce DNA synthesis in cultured cells is not understood, but morphological changes Induced by growth factors have been used as clues to Intracellular messengers responsible for growth stimulation. One such morphological change has been the transient disappearance of the primary cilium, a “9 + 0” cilium formed by the perinuclear centriole in interphase cells. Since calcium ionophore A23187 also produced both mitogenesis and ciliary changes, microtubule depolymerization might explain ciliary disappearance monitored by indirect immunofluorescence with anti-tubulin antibody. However, complete resorption and subsequent reformation of the primary cilium occurs at mitosis, and might also account for ciliary disappearance induced by growth factors. To settle this issue, we investigated the ultrastructure of the primary cilium using serial thin-section electron microscopy of quiescent BALB/c 3T3 cells before and after stimulation with serum.


2002 ◽  
Vol 69 ◽  
pp. 47-57 ◽  
Author(s):  
Catherine L. R. Merry ◽  
John T. Gallagher

Heparan sulphate (HS) is an essential co-receptor for a number of growth factors, morphogens and adhesion proteins. The biosynthetic modifications involved in the generation of a mature HS chain may determine the strength and outcome of HS–ligand interactions. These modifications are catalysed by a complex family of enzymes, some of which occur as multiple gene products. Various mutant mice have now been generated, which lack the function of isolated components of the HS biosynthetic pathway. In this discussion, we outline the key findings of these studies, and use them to put into context our own work concerning the structure of the HS generated by the Hs2st-/- mice.


2005 ◽  
Vol 173 (4S) ◽  
pp. 156-156
Author(s):  
Kazuya Suzuki ◽  
Tsutomu Nishiyama ◽  
Noboru Hara ◽  
Vladimir Bilim ◽  
Kazutoshi Yamana ◽  
...  

2004 ◽  
Vol 171 (4S) ◽  
pp. 365-365
Author(s):  
Tamer M. Said ◽  
Shyam Allamaneni ◽  
Kiran P. Nallella ◽  
Rakesh K. Sharma ◽  
Mohamed A. Bedaiwy ◽  
...  
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