Mechanisms of reduced body growth in the pubertal feminized male rat: unbalanced estrogen and androgen action on the somatotropic axis.
It is well known that the sex difference in body growth at puberty is modulated by a complex interplay between sex steroids and somatotropic axis; however, the exact role played by sex steroids remains a matter of controversy. The aim of this study was to assess the mechanisms by which sex steroids regulate body growth during pubertal development. Flutamide, a non-steroid-blocking androgen receptor, was subcutaneously administered to 30-d-old male Wistar rats for 4 wk. The blockade of the androgen receptor led to a marked elevation in serum testosterone and an increment in serum estradiol. Flutamide administration decreased body weight gain, serum IGF-I levels, hepatic IGF-I mRNA, and GH receptor mRNA content. There were no significant changes in serum GH concentration, pituitary GH reserve, and pituitary GH mRNA content. Flutamide lowered hypothalamic somatostatin mRNA content and augmented hypothalamic immunoreactive somatostatin stores, but did not alter hypothalamic immunoreactive GH-releasing factor stores. Our findings indicate that during pubertal development of the male rat, the imbalance between androgen and estrogen actions determines an abnormal somatic growth, which is at least partly exerted through the peripheral or hepatic modification of the somatotropic axis that occurs under the high or exclusive action of estrogens. Potential implication of coincident sex-specific regulated mode of pulsatile GH secretion cannot be excluded from this random serum GH sample study.
Pazos
F
F
Endocrine Service, Hospital Ramón y Cajal, Madrid, Spain.
Sánchez-Franco
F
F
Balsa
J A
JA
Escalada
J
J
Palacios
N
N
Cacicedo
L
L
D000375:Aging; D059002:Androgen Receptor Antagonists; D000818:Animals; D005485:Flutamide / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011986:Receptors, Somatotropin / Q000235:genetics; D012741:Sexual Maturation / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects*
D059002:Androgen Receptor Antagonists; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D005485:Flutamide; D013006:Growth Hormone