title: Growth response and androgen receptor expression in seminal vesicles from aging transgenic mice expressing human or bovine growth hormone genes.
abstract: Previous work has shown that expression of human (h) GH in transgenic mice is associated with significant age-related enlargement of seminal vesicles. To further explore this aberrant growth activity, we have characterized seminal vesicles from various GH transgenic lines and examined their androgen receptor (AR) content and distribution. Six groups of animals were initially studied: young adult (3-5 months) control mice, old (greater than 12 months) control mice, young adult hGH transgenic mice, old hGH transgenics, young adult bovine (b) GH transgenics, and old bGH transgenic mice. Young transgenic mice (hGH and bGH) possessed seminal vesicles with similar relative weights, DNA and protein contents, and AR levels as nontransgenic littermates. Histologically, the glands appeared similar. With aging, the hGH transgenic seminal vesicles exhibited massive stromal hyperplasia, whereas the glands from controls and bGH transgenic mice did not show this response. Seminal vesicles from old hGH mice presented with a marked increase in cell number (DNA content) and a marked decrease in cell size and/or glandular secretions (protein/DNA ratio) compared to those from old controls and young hGH transgenic mice. Tissue AR content was markedly reduced in old hyperplastic hGH seminal vesicles compared to that in seminal vesicles from young hGH transgenics, old controls, and old bGH transgenic mice. Immunohistochemistry indicated the absence of AR in the proliferating stromal cells, whereas acinar epithelial cells showed similar or moderately reduced AR staining intensity compared to control seminal vesicles. To examine whether the above results may be due to insertional mutagenesis rather than hGH itself, two additional GH transgenic lines were examined. Aged transgenic mice expressing bGH with an alternate promoter possessed seminal vesicle weights that were not different from those of old controls, whereas aged transgenic mice expressing an hGH. V gene (variant gene, placental origin) possessed significantly larger vesicles than the controls, which further suggests that vesicular hyperplasia is specifically related to hGH. To assess androgen responsiveness, aged control and hGH transgenic mice were castrated and examined after 15 days. While control seminal vesicles significantly decreased in size, glands from transgenic mice did not. Regressive changes were observed in the remaining epithelium of hGH transgenic mice; however, stromal tissue exhibited no response to androgen withdrawal. The present results suggest that the aging-associated seminal vesicle hyperplasia in hGH transgenic mice is a result of a massive increase in stromal tissue that is low or devoid of AR, suggesting a loss of direct androgen regulation.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Obstetrics and Gynecology, Humana-Michael Reese Hospital, University of Illinois School of Medicine, Chicago 60616.
authors.forename: G S
authors.initials: GS
authors.lastname: Prins
authors.forename: M
authors.initials: M
authors.lastname: Cecim
authors.forename: L
authors.initials: L
authors.lastname: Birch
authors.forename: T E
authors.initials: TE
authors.lastname: Wagner
authors.forename: A
authors.initials: A
authors.lastname: Bartke
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009929:Organ Size; D011944:Receptors, Androgen / Q000378:metabolism*; D012669:Seminal Vesicles / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D013006:Growth Hormone