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Androgen‐induced norepinephrine release mediating guinea pig seminal vesicle smooth muscle proliferation: Potential role of pre‐synaptic α 2 ‐adrenoceptors
Author(s) -
Kim Julie M.,
Cole Dennis J.,
Franklin Grant L.,
Mawhinney Michael G.
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10273
Subject(s) - endocrinology , medicine , androgen , basal (medicine) , biology , norepinephrine , androgen receptor , hormone , dopamine , diabetes mellitus , prostate cancer , cancer
BACKGROUND Recent studies from our laboratory have demonstrated that androgen‐induced basal norepinephrine (NE) release is responsible for the onset of proliferation in seminal vesicle smooth muscle (SVM) cells during early puberty. With subsequent sexual maturation, SVM was irreversibly differentiated to an androgen‐resistant‐amitotic state in which basal NE release remained elevated and resistant to androgen withdrawal or repletion. Based on these findings, we hypothesized that this irreversible elevation of basal NE release during pubertal development is caused, at least in part, by the down‐regulation of pre‐synaptic NE feedback inhibition, secondary to irreversible reduction in the expression of neuronal (pre‐synaptic) α 2 ‐adrenoceptors. Functional α 2 ‐adrenoceptors are selectively localized to pre‐synaptic sites in SVM. METHODS To test this hypothesis, we employed ligand binding techniques with [ 3 H]RX821002, an antagonist which labeled all α 2 ‐adrenoceptor sub‐types. Initial experiments focused on analysis of competitor specificity to identify the predominant α 2 ‐adrenoceptor sub‐type in SVM. Subsequently, we quantified the changes in the receptor concentration (B max ) for [ 3 H]RX821002 at the point of maximal dihydrotestosterone (DHT)‐induced change in basal NE release. RESULTS Based on competitor specificity for [ 3 H]RX821002, the α 2D ‐adrenoceptor sub‐type predominated in SVM. We treated pre‐pubertal castrate animals with DHT for 7 days, which was previously demonstrated to maximally induce basal NE release. This treatment reduced the pre‐synaptic α 2 ‐adrenoceptor B max 4‐fold. In animals which had been castrated as adults, the B max for [ 3 H]RX821002 remained irreversibly suppressed. CONCLUSIONS The DHT‐dependent reduction in the α 2 ‐adrenoceptor concentration is consistent with the developmental pattern of increased basal NE release. These findings support the hypothesis that the down‐regulation of pre‐synaptic NE feedback is mechanistically involved in the irreversible elevation of basal NE release. NE mediates proliferation in SVM in early pubertal development. Thus, the androgen‐dependent pubertal growth of smooth muscle cells may be indirectly controlled at the level of neurotransmission. Prostate 57: 51–56, 2003. © 2003 Wiley‐Liss, Inc.