Augmented hypothalamic proopiomelanocortin gene expression with pubertal development in the male rat: evidence for an androgen receptor-independent action.
To investigate the mechanism(s) during pubertal development by which androgens alter hypothalamic proopiomelanocortin (POMC) gene expression and beta-endorphin content, we used the technique of in situ hybridization histochemistry and the androgen-insensitive testicular feminized (Tfm) rat. We evaluated POMC mRNA levels in the arcuate nuclei and periarcuate regions of 12 coronal brain slices from prepubertal (age, 30 days) and adult (age, 60 days) normal male and Tfm rats (n = 4 for each group). Hybridizations were performed using an 35S-radiolabeled oligonucleotide probe complementary to a 30-base sequence within POMC mRNA. The tissue sections were sequentially exposed to x-ray film and photographic emulsion with subsequent analysis by both densitometry and computer-assisted grain counting. beta-Endorphin was measured in hypothalamic tissue blocks from similar animals in each of the four experimental groups. The results of densitometry and grain counting were consistent and revealed an increase in POMC mRNA with pubertal development in both the male and Tfm animals. The concentration of hypothalamic beta-endorphin was greater for the adult Tfm animals than for all other groups, which did not differ from each other. These results suggest that androgens may stimulate POMC gene transcription by their action through estrogen receptors after conversion by aromatase. Alternatively, additional pubertal factors may be responsible for act directly through their respective receptors to alter translation, posttranslational processing, or secretion of beta-endorphin, resulting in diminished intracellular hypothalamic peptide concentration.
Kerrigan
J R
JR
Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908.
Martha
P M
PM
Krieg
R J
RJ
Queen
T A
TA
Monahan
P E
PE
Rogol
A D
AD
D000818:Animals; D001835:Body Weight; D005786:Gene Expression Regulation; D012739:Gonadal Steroid Hormones / Q000097:blood; D006651:Histocytochemistry; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009693:Nucleic Acid Hybridization; D009994:Osmolar Concentration; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D051381:Rats; D011944:Receptors, Androgen / Q000502:physiology*; D001615:beta-Endorphin / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin