Androgens modulate epidermal growth factor receptor levels in the rat ventral prostate.
In order to further understand the factors which influence the normal or pathologic growth of the prostate, we have characterized the receptor for epidermal growth factor (EGF) in the rat ventral prostate and have studied the hormonal regulation in this receptor. EGF binds to a single class of saturable, high affinity binding sites in total prostatic homogenate. Scatchard analysis of the binding data reveals an apparent dissociation constant (KD) of 0.93 +/- 0.08 nM and a number of sites of 4.01 +/- 0.24 fmol per mg protein. Among the peptides tested, only native EGF can displace bound [125I]EGF. Castration stimulates the concentration of prostatic EGF receptors from 25.5 +/- 3.0 to 43.4 +/- 5.4 fmol/100 mg tissue in intact and castrated animals, respectively (P less than 0.01). Treatment of castrated rats with dihydrotestosterone (DHT) inhibits the rise in prostatic EGF receptor concentration induced by orchiectomy, while estradiol, progesterone or the dopaminergic agonist CB-154, have no effect. Combined administration of DHT with the other above-mentioned steroids or CB-154 does not modify the inhibition of prostatic EGF receptor concentration induced by the androgen in castrated animals. When the data are expressed as changes in EGF receptor number in the total prostate, DHT treatment reverses the inhibitory effect induced by castration and yields an EGF binding capacity comparable to that measured in intact animals. Chronic treatment with a pure antiandrogen or a potent LHRH agonist (LHRH-A) alone has no significant effect on EGF receptor concentration in prostatic tissue, although, secondary to a reduction in prostatic weight, total prostatic EGF binding capacity is reduced following antiandrogen or LHRH-A treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
St-Arnaud
R
R
Department of Molecular Endocrinology, Le Centre Hospitalier de l'Université Laval, Quebec, Que., Canada.
Poyet
P
P
Walker
P
P
Labrie
F
F
D000728:Androgens / Q000502:physiology*; D000818:Animals; D066246:ErbB Receptors / Q000502:physiology*; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D000728:Androgens; D066246:ErbB Receptors