Adipocyte Accumulation in Penile Corpus Cavernosum of the Orchiectomized Rabbit: A Potential Mechanism for Veno‐occlusive Dysfunction in Androgen Deficiency

Abstract

Androgens are deemed to be critical for the development, growth, and maintenance of penile tissue as well as for erectile function. Androgens are also reported to inhibit differentiation of stroma progenitor cells into adipocytes and promote differentiation into smooth muscle. The objective of this study was to investigate whether androgen deprivation results in accumulation of adipocytes in the corpus cavernosum. Mature, New Zealand white male rabbits were subjected to sham surgery (control) or orchiectomy. Two weeks after surgery, erectile function was assessed by monitoring changes in intracavernosal blood pressure (ICP) in response to pelvic nerve stimulation. All ICP measurements were normalized to the mean systemic arterial blood pressure. In parallel studies, penile cross sections from control and orchiectomized rabbits were fixed and stained with either Masson's trichrome or hematoxylin and eosin to assess smooth muscle and connective tissue content. Alternatively, tissue sections were stained with Toluidine blue to assess accumulation of fat-containing cells. Orchiectomy resulted in loss of erectile function and penile atrophy, associated with reduced trabecular smooth muscle and increased connective tissue content. Most strikingly, tissue from orchiectomized animals exhibited accumulation of fat-containing cells (adipocytes) in the subtunical region of the corpus cavernosum. We hypothesize that androgen deprivation promotes differentiation of progenitor stroma cells into an adipogenic lineage producing fat-containing cells, thus altering erectile function.

Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction

“…In addition to the alterations in smooth muscle and connective tissue, fat-containing cells have been observed in the subtunical region of penile tissue sections from orchiectomized animals [31]. The alterations in cavernosal tissue composition and structure were accompanied by a reduced erectile response to pelvic nerve stimulation [11,31].…”

“…The alterations in cavernosal tissue composition and structure were accompanied by a reduced erectile response to pelvic nerve stimulation [11,31]. It is interesting to speculate that the presence of fat cells in the subtunical region of the corpus cavernosum may contribute to venous leakage in the orchiectomized or androgen-deficient animal.…”

The relationship between hypogonadism and erectile dysfunction

“…This basic model was produced by Traish et al 18,19 It was comprised of stimulating the pelvic nerve of an animal and monitoring the subsequent erection. A castrated animal did not respond, but erectile function was restored after replacement of T.…”

“…In addition to changes in connective tissue and smooth muscle Traish et al 19 revealed hollow cellular structures in the subtunical region of the corpus cavernosum that were distinct from cavernous spaces in an orchidectomized rat model. Those hollow cells resembled adipocytes and were consistently present in tissues of orchidectomized animals but were absent from tissues of control animals.…”

Emerging concepts in erectile preservation following radical prostatectomy: a guide for clinicians

“…41 Traish et al performed a simple and elegant experiment with control and orchiectomized rabbits. Their results demonstrated that study group animals developed pockets of adipocytes throughout the cavernosal smooth muscle matrix.…”