Biomedical subjects

Noel N Kim

Publications and source records attributed to Noel N Kim.

At least 19 recordsLinked to original sources

PubMed2006

Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat.

BACKGROUND: Tamoxifen, a selective estrogen receptor modulator with both estrogenic and anti-estrogenic activity, is widely used as adjuvant therapy in breast cancer patients. Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity. There have been limited investigations of the effect of tamoxifen on estrogen-dependent peripheral genital arousal responses. The objective of this study was to investigate the effects of tamoxifen on vaginal physiology in the rat. METHODS: Female Sprague-Dawley rats were subjected to sham surgery or bilateral ovariectomy. After 2 weeks, sham-operated rats were implanted with subcutaneous osmotic infusion pumps containing vehicle (control) or tamoxifen (150 microg/day). Ovariectomized rats were similarly infused with vehicle. After an additional 2 weeks, vaginal blood flow responses to pelvic nerve stimulation were measured by laser Doppler flowmetry and vaginal tissue was collected for histological and biochemical assay. RESULTS: Tamoxifen treatment did not change plasma estradiol concentrations relative to control animals, while ovariectomized rats exhibited a 60% decrease in plasma estradiol. Tamoxifen treatment caused a significant decrease in mean uterine weight, but did not alter mean vaginal weight. Vaginal blood flow was significantly decreased in tamoxifen-infused rats compared to controls. Similar to ovariectomized animals, estrogen receptor binding was increased and arginase enzyme activity was decreased in tamoxifen-infused rats. However, different from control and ovariectomized animals, the vaginal epithelium in tamoxifen-infused rats appeared highly mucified. Periodic acid-Schiff staining confirmed a greater production of carbohydrate-rich compounds (e.g. mucin, glycogen) by the vaginal epithelium of tamoxifen-infused rats. CONCLUSION: The observations suggest that tamoxifen exerts both anti-estrogenic and pro-estrogenic effects in the vagina. These physiological alterations may eventually lead to vaginal atrophy and compromise sexual function.

Journal Article↗

PubMed2006

Streptozotocin-induced diabetes in the rat is associated with changes in vaginal hemodynamics, morphology and biochemical markers.

BACKGROUND: Diabetes is associated with declining sexual function in women. However, the effects of diabetes on genital tissue structure, innervation and function remains poorly characterized. In control and streptozotocin-treated female rats, we investigated the effects of diabetes on vaginal blood flow, tissue morphology, and expression of arginase I, endothelial nitric oxide synthase (eNOS) and cGMP-dependent protein kinase (PKG), key enzymes that regulate smooth muscle relaxation. We further related these changes with estrogen receptor alpha (ERalpha) and androgen receptor (AR) expression. RESULTS: In addition to significantly elevated blood glucose levels, diabetic rats had decreased mean body weight, lower levels of plasma estradiol, and higher plasma testosterone concentration, compared to age-matched controls. Eight weeks after administration of buffer (control) or 65 mg/kg of streptozotocin (diabetic), the vaginal blood flow response to pelvic nerve stimulation was significantly reduced in diabetic rats. Histological examination of vaginal tissue from diabetic animals showed reduced epithelial thickness and atrophy of the muscularis layer. Diabetic animals also had reduced vaginal levels of eNOS and arginase I, but elevated levels of PKG, as assessed by Western blot analyses. These alterations were accompanied by a reduction in both ERalpha and AR in nuclear extracts of vaginal tissue from diabetic animals. CONCLUSION: In ovariectomized (estrogen deficient) animals, previous reports from our lab and others have documented changes in blood flow, tissue structure, ERalpha, arginase I and eNOS that parallel those observed in diabetic rats. We hypothesize that diabetes may lead to multiple disruptions in sex steroid hormone synthesis, metabolism and action. These pathological events may cause dramatic changes in tissue structure and key enzymes that regulate cell growth and smooth muscle contractility, ultimately affecting the genital response during sexual arousal.

Animals↗

PubMed2006

Dose-response relationship between testosterone and erectile function: evidence for the existence of a critical threshold.

Androgens play an important role in erectile function. However, the dose-response relationship between plasma testosterone levels and penile erection remains unclear. Intact (sham operated) or bilaterally orchiectomized, mature male Sprague-Dawley rats were used. Two weeks after surgery, rats were infused continuously with either vehicle (polyethyleneglycol) or varying doses of testosterone (44, 88, 220, or 440 mug/day) for 14 days using subcutaneous osmotic infusion pumps (study 1). In a separate study, 4 weeks after surgery, rats were infused with a lower range of testosterone doses (11, 22, or 44 mug/day) for 14 days (study 2). In the first study, intact rats had a mean plasma testosterone concentration of 0.56 +/- 0.12 ng/mL ( approximately 1.9 nM), as determined by standard radioimmunoassay. In the second study, a more sensitive enzyme-linked immunoassay was used to measure the lower testosterone levels. Using this assay, intact rats had a mean plasma testosterone concentration of 2.02 +/- 0.59 ng/mL. Intracavernosal pressure measurements indicated that orchiectomy resulted in a significant reduction in erectile function, when compared to intact animals, whereas testosterone infusion restored erectile function to varying degrees. Erectile function was maintained by a wide range of systemic testosterone levels as low as 10%-12% of normal physiological plasma concentrations. Below these concentrations, erectile function was significantly and positively correlated with testosterone plasma levels in a dose-dependent manner. Interestingly, prostate tissue mass was positively correlated to plasma testosterone levels across all concentrations examined. Protein expression of neural nitric oxide synthase (nNOS) and phosphodiesterase type 5 (PDE 5) was reduced in penile tissue from orchiectomized animals and increased in testosterone-infused animals, as assessed by Western blot analyses. We suggest that testosterone at levels approaching one-tenth normal physiological plasma concentration may represent a threshold value, below which erectile function declines in a dose-dependent fashion. However, different androgen-dependent tissues may exhibit varying sensitivities to circulating testosterone with regard to growth and function.

Animals↗

PubMed2004

Binding characteristics of [3H]delta(5)-androstene-3beta,17beta-diol to a nuclear protein in the rabbit vagina.

In this study, we investigated the binding characteristics of [3H]Delta(5)-androstene-3beta,17beta-diol to rabbit vaginal cytosolic and nuclear extracts and in freshly excised intact tissue strips. [3H]delta(5)-Androstene-3beta,17beta-diol bound to a protein(s) in the vaginal nuclear extract with high affinity (K(d)=3-5 nM) and limited capacity (50-100 fmol/mg protein). No specific binding was detected in the cytoplasmic extracts. Competitive binding studies showed that binding of [3H]delta(5)-androstene-3beta,17beta-diol was effectively displaced with unlabeled delta(5)-androstene-3beta,17beta-diol but not with dehydroepiandrosterone, testosterone, dihydrotestosterone, triamcinolone acetonide, or progesterone. However, estradiol at high concentrations partially displaced bound [3H]delta(5)-androstene-3beta,17beta-diol. Incubation of freshly excised vaginal tissue strips with [3H]delta(5)-androstene-3beta,17beta-diol in the absence or presence of excess unlabeled delta(5)-androstene-3beta,17beta-diol for 1h at 37 degrees C resulted in specific binding to a soluble macromolecule in the nuclear KCl extracts. In addition, quantitative measurement of estrogen receptor, androgen receptor and delta(5)-androstene-3beta,17beta-diol binding protein was performed by equilibrium ligand binding assays using extracts of distal vaginal tissue from intact animals or ovariectomized animals treated for 2 weeks with vehicle, estradiol, testosterone, or estradiol plus testosterone. These changes in steroid hormone levels resulted in opposing trends between the estrogen receptor and delta(5)-androstene-3beta,17beta-diol binding protein, suggesting that delta(5)-androstene-3beta,17beta-diol binding protein is regulated differently by the hormonal milieu than the estrogen receptor. These data suggest that rabbit vaginal tissue expresses a novel binding protein which specifically binds delta(5)-androstene-3beta,17beta-diol and is distinct from the androgen and estrogen receptors.

Androstane-3,17-diol↗

PubMed2004

Role of arginase in the male and female sexual arousal response.

The NO-cGMP pathway plays a key role in the male and female genital sexual arousal response. Nitric oxide synthase (NOS) utilizes L-arginine and oxygen as substrates to produce nitric oxide (NO) and citrulline. Arginase is a metalloenzyme that catalyzes the hydrolysis of L-arginine to produce L-ornithine and urea. It is proposed that arginase competes for L-arginine and reduces NOS activity in genital tissues, thus modulating sexual function. Using 2 transition state analogue inhibitors of arginase, 2(S)-Amino-6-boronohexanoic acid (ABH) and S-(2-boronoethyl)-L-cysteine (BEC), we have characterized arginase activity in penile and vaginal tissue. Neither of these inhibitors has activity against NOS. Thus, ABH and BEC are useful compounds for examining the role of arginase in genital tissue physiology, without directly influencing NOS activity. We present data to suggest that arginase may regulate NO production by competing for endogenous pools of L-arginine. In this fashion, arginase is an indirect regulator of penile and vaginal blood flow and specific arginase inhibitors may improve genital blood flow during sexual arousal. As evidenced by the upregulation of arginase in specific disease states, its distribution in the vagina, and its modulation by sex steroid hormones, this enzyme may also participate in numerous other physiological and pathophysiological processes, such as tissue growth, fibrosis, and immune function.

Animals↗

PubMed2004

An in vivo rat model to investigate female vaginal arousal response.

PURPOSE: We established a rat model to investigate the female vaginal arousal response and the role of the nitric oxide (NO) pathway on vaginal blood flow in vivo. MATERIALS AND METHODS: Vaginal blood flow changes induced by pelvic nerve stimulation (PNS) in female Sprague-Dawley rats were determined by laser Doppler flowmetry. Frequency response data were determined in each animal. In addition, changes in vaginal blood flow were measured after intravenous administration of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) or the phosphodiesterase type 5 inhibitor sildenafil in response to PNS at submaximal frequency. Changes in blood flow were evaluated by comparing the area under the curve of each response. RESULTS: Reproducible frequency dependent increases in vaginal blood flow were observed in response to PNS. Administration of L-NAME (a NO synthase inhibitor) resulted in significant attenuation (25.6% to 18.2% vs control at 30 minutes, p <0.00001) of the PNS induced increase in vaginal blood flow. In contrast, sildenafil administration significantly increased PNS induced vaginal blood flow (166.9% +/- 25.8% vs control at 30 minutes, p <0.00001). CONCLUSIONS: Our data suggest that the rat is a useful and reliable animal model for investigating the vaginal arousal response. In addition, we used this model to demonstrate the important role of the NO-cyclic guanosine monophosphate pathway in vaginal arousal.

Animals↗

PubMed2004

Modulation of rat vaginal blood flow and estrogen receptor by estradiol.

PURPOSE: The effects of subphysiological and physiological levels of estradiol on vaginal blood flow and estrogen receptor were investigated. MATERIALS AND METHODS: Intact or ovariectomized female Sprague-Dawley rats were used. Two weeks after surgery rats were infused with vehicle (polyethyleneglycol), or estradiol at subphysiological (5 microg daily) or physiological (15 microg daily) concentrations for 14 days using osmotic pumps. Changes in vaginal blood flow elicited by pelvic nerve stimulation were assessed by laser Doppler flowmetry. Total levels of functional estrogen receptor were determined by radioligand binding and Western blot analyses were used to assess estrogen receptor (ER) alpha protein. RESULTS: Mean plasma estradiol concentration +/- SEM decreased by 63% in the vehicle group (intact 36.5 +/- 10.3 pg/ml). The subphysiological and physiological estradiol groups had plasma levels that were 55% and 83% of the intact group, respectively. Uterine and vaginal wet weight, and vaginal blood flow were significantly decreased in the vehicle group and normalized by physiological levels of estradiol. However, vaginal blood flow was significantly greater in the subphysiological estradiol group compared to intact animals. Specific binding of [H]estradiol in vaginal tissue extracts from intact rats was 0.51 fmol/mg protein and it was increased 30-fold in the vehicle group. ER binding in vaginal tissue in the physiological estradiol group decreased to levels that were comparable to those in intact animals, whereas estrogen receptor binding remained elevated in the subphysiological estradiol group. These changes were paralleled by ERalpha protein levels. CONCLUSIONS: Estradiol is crucial for maintaining optimal vaginal blood flow in the rat. Lower levels of plasma estradiol trigger compensatory ERalpha up-regulation.

Animals↗

PubMed2003

Human arginase II: crystal structure and physiological role in male and female sexual arousal.

Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. The X-ray crystal structure of a fully active, truncated form of human arginase II complexed with a boronic acid transition state analogue inhibitor has been determined at 2.7 A resolution. This structure is consistent with the hydrolysis of l-arginine through a metal-activated hydroxide mechanism. Given that human arginase II appears to play a role in regulating l-arginine bioavailability to NO synthase in human penile corpus cavernosum smooth muscle, the inhibition of human arginase II is a potential new strategy for the treatment of erectile dysfunction [Kim, N. N., Cox, J. D., Baggio, R. F., Emig, F. A., Mistry, S., Harper, S. L., Speicher, D. W., Morris, S. M., Ash, D. E., Traish, A. M., and Christianson, D. W. (2001) Biochemistry 40, 2678-2688]. Since NO synthase is found in human clitoral corpus cavernosum and vagina, we hypothesized that human arginase II is similarly present in these tissues and functions to regulate l-arginine bioavailability to NO synthase. Accordingly, hemodynamic studies conducted with a boronic acid arginase inhibitor in vivo are summarized, suggesting that the extrahepatic arginase plays a role in both male and female sexual arousal. Therefore, arginase II is a potential target for the treatment of male and female sexual arousal disorders.

Amino Acid Sequence↗

PubMed2003

Cocaine and ephedrine-induced priapism: case reports and investigation of potential adrenergic mechanisms.

OBJECTIVES: To investigate the direct effect of ephedrine and cocaine on neurogenic contraction of penile trabecular smooth muscle. We also provide three case reports of patients who developed priapism secondary to using either cocaine or nonprescription weight loss formulations containing ephedrine. The use/abuse of cocaine has been associated with priapism. In addition, anecdotal evidence suggests that priapism may result from ephedrine use. However, the effects of cocaine and ephedrine on adrenergic regulation of cavernosal tissue and the potential role of sympathetic dysregulation in the development of priapism have not been studied. METHODS: Isolated rabbit penile cavernosal tissue strips in organ bath preparations were subjected to electrical field stimulation (EFS) at varying frequencies (5 to 40 Hz) in the absence or presence of ephedrine (60 microg/mL) or cocaine (10 microM). Tissues were then subjected to EFS every 30 minutes for up to 20 hours. RESULTS: Ephedrine and cocaine initially caused contractions in cavernosal tissue strips that persisted for several hours. EFS-induced contractions became attenuated over time in tissues treated with ephedrine or cocaine. Eventually, the contractile responses to EFS were not distinguishable from the basal tone, although the tissues remained responsive to exogenous phenylephrine. CONCLUSIONS: Functional activation of alpha-adrenergic receptors on trabecular smooth muscle does not appear to be impaired with prolonged cocaine or ephedrine exposure. However, chronic use of cocaine or ephedrine may deplete norepinephrine from sympathetic nerve terminals, leading to priapism.

Adrenergic alpha-Agonists↗

PubMed2003

Effects of ovariectomy and estrogen replacement on basal and pelvic nerve stimulated vaginal lubrication in an animal model.

The goal of this study was to investigate the effects of ovariectomy and estrogen replacement on vaginal tissue integrity and vaginal lubrication in basal conditions and in response to pelvic nerve stimulation (PNS). Two weeks after ovariectomy, female New Zealand White rabbits were administered vehicle or estradiol (200 micrograms/day) for an additional 2 weeks. Ovariectomy caused significant vaginal atrophy and diminished vaginal lubrication in the basal state and after PNS, compared to intact controls. Estrogen replacement normalized lubrication values and tissue wet weight to control levels. In conclusion, vaginal tissue integrity and lubrication are diminished by ovariectomy and are normalized by estrogen replacement.

Animals↗

PubMed2003

A review of the physiology and pharmacology of peripheral (vaginal and clitoral) female genital arousal in the animal model.

PURPOSE: We review contemporary scientific data concerning the physiology and pharmacology of peripheral female genital arousal responses in the animal (rabbit and rat) model. MATERIALS AND METHODS: We reviewed the contemporary literature and our research studies concerning physiology and pharmacology of peripheral genital arousal from 3 experimental animal models, including genital smooth muscle cell culture, genital strip organ bath and in vivo animal model studies. RESULTS: Nitric oxide (NO) appears to be a key pathway mediating clitoral smooth muscle relaxation. In the vagina NO appeared to have a more controversial role in mediating vaginal muscularis smooth muscle relaxation. Vasoactive intestinal polypeptide induced vaginal smooth muscle relaxation. Functional alpha-adrenergic receptors were expressed in the clitoris and vagina, and mediated norepinephrine induced genital smooth muscle contraction. Androgens and estrogens modulated distinct physiological responses in vagina, and androgens facilitated vaginal smooth muscle relaxation. Papaverine hydrochloride, a smooth muscle relaxant, and phentolamine mesylate, an alpha-blocker, administered into the vaginal spongy muscularis layer increased vaginal wall pressure and vaginal blood flow. Sildenafil caused significant increases in genital (clitoral and vaginal) blood flow and vaginal lubrication in intact and ovariectomized animals. This response was more pronounced in animals treated with estradiol, suggesting that the NO cyclic guanosine monophosphate pathway is involved in the physiological mechanism of female genital arousal and that sildenafil facilitates this response in an in vivo animal model. CONCLUSIONS: To achieve improved understanding of the biological aspects of female sexual function, further research is needed in the physiology and pharmacology of peripheral (clitoral and vaginal) genital arousal in the animal model.

Animals↗

PubMed2002

Biochemical and functional characterization of alpha-adrenergic receptors in the rabbit vagina.

Vascular and non-vascular smooth muscle within the vagina mediate important physiological changes during sexual arousal in women. In this study, we have characterized alpha-adrenergic receptors (AR) in rabbit vagina by assessment of radioligand binding, contractility of isolated tissue strips and genital hemodynamics. [3H]Prazosin and [3H]RX821002 (alpha-1 and alpha-2 AR selective antagonists) bound to rabbit vaginal membrane preparations with high affinity and limited capacity. Competition binding assays using both non-selective and subtype selective ligands for AR (phentolamine, prazosin, delequamine, rauwolscine and UK14304) further confirmed the presence of alpha-1 and alpha-2 AR in vaginal tissue. In organ bath preparations of vaginal tissue strips, norepinephrine-induced contraction was attenuated by alpha-1 and alpha-2 AR antagonists (prazosin, tamsulosin, delequamine and phentolamine). In anesthetized rabbits, intravaginal injection of the alpha-1 AR selective antagonist REC 15/2615 (50 and 100 microg/kg) caused a 2 to 3-fold increase in genital tissue oxyhemoglobin (OHb) concentration. Similar increases in tissue OHb were observed with intravaginal injection of phentolamine (500 microg/kg) or a tri-mixture of vasodilators (PGE1, papaverine, phentolamine). REC 15/2615, phentolamine or the tri-mixture also enhanced the amplitude and/or duration of change in genital tissue OHb after pelvic nerve stimulation. Thus, vaginal tissue expresses functional alpha-1 and alpha-2 AR, which modulate vaginal smooth muscle contractility and genital engorgement.

Administration, Intravaginal↗

PubMed2002

Biology of female sexual function.

Although the psychosocial and relationship aspects of female sexuality have been extensively investigated, studies concerning the anatomy, physiology and pathophysiology of female sexual function and dysfunction are limited. The paucity of biologic data may be attributed to a lack of reliable experimental models and tools for investigating female sexual function and to limited funding, which is critical for developing experimental approaches. Research efforts by several investigators in different laboratories have been establishing experimental models needed for investigating the physiologic mechanisms involved in the genital arousal response of sexual function. These experimental models have permitted assessment of genital hemodynamics, vaginal lubrication, regulation of genital smooth muscle contractility and signaling pathways, providing preliminary information about the role of neurotransmitters and sex steroid hormones in sexual function. Further research is needed to define the neurotransmitters responsible for vaginal smooth muscle relaxation and the role of sex steroid hormones and their receptors in modulating genital hemodynamics, smooth muscle contractility, and neurotransmitter receptor expression. Finally, a global and integral understanding of the biologic aspects of female sexual function requires investigation of the vascular, neurologic (central and peripheral), and structural components of this extremely complex physiologic process.

Animals↗

PubMed2002

Biochemical and physiological mechanisms of female genital sexual arousal.

Limited studies are available concerning physiological and biochemical mechanisms involved in female sexual function and dysfunction. The paucity of physiological and biochemical data pertaining to genital sexual arousal function is attributed, in part, to lack of reliable experimental models and tools for the investigation of female sexual arousal. This review summarizes research efforts from a number of laboratories in which several experimental models have been established. These include the development of in vivo animal models, organ bath studies, and the establishment of cell cultures. The availability of such experimental model systems have facilitated efforts aimed at defining the neurotransmitters responsible for vaginal smooth muscle relaxation, the role of sex steroid hormones and their receptors in modulating genital hemodynamics, smooth muscle contractility, and neurotransmitter receptor expression. A comprehensive and integral understanding of female sexual function requires detailed investigation of the vascular, neurological (central and peripheral), and structural components of this complex physiological process.

Animals↗

PubMed2002

Effects of ovariectomy and estrogen and androgen treatment on sildenafil-mediated changes in female genital blood flow and vaginal lubrication in the animal model.

OBJECTIVE: Our purpose was to investigate the effects of ovariectomy and estradiol and testosterone treatment on sildenafil- induced changes in genital hemodynamics and vaginal lubrication. STUDY DESIGN: Female New Zealand White rabbits were either kept intact or underwent ovariectomy. Two weeks after ovariectomy, animals were treated with vehicle, testosterone, or a combination of estradiol and testosterone for 14 days. Genital hemodynamics and vaginal lubrication were recorded at the end of the treatment period. RESULTS: Ovariectomy caused a marked decrease in vaginal lubrication but did not significantly alter genital hemodynamics. In contrast to testosterone treatment of ovariectomized animals, estradiol treatment significantly increased genital blood flow and vaginal lubrication above that observed in control animals. Sildenafil administration caused a significant increase in genital hemodynamics irrespective of the hormonal status. CONCLUSION: This study suggests that estradiol but not testosterone modulates genital hemodynamics and that sildenafil enhances genital blood flow irrespective of hormonal status.

Animals↗

PubMed2002

Androgen replacement therapy with dehydroepiandrosterone for androgen insufficiency and female sexual dysfunction: androgen and questionnaire results.

During our evaluations of women with sexual dysfunction, we have seen many with low interest, arousal, and orgasmic capabilities with associated personal distress and diminished genital sensation and blood flow following sexual stimulation. Laboratory evaluation of these women has revealed normal estrogen but androgen values that were either below or in the lower quartile of the physiologic range. Androgen insufficiency and sexual dysfunction have been the working diagnoses in these women. Although many treatment options currently are available for this syndrome, there are limited data concerning safety and efficacy. The aim of this retrospective, Institutional Review Board (IRB)--approved, single-institution study was to report on the androgen and questionnaire results from a series of patients who underwent androgen replacement therapy with dehydroepiandrosterone for treatment of androgen insufficiency and sexual dysfunction. This study revealed that there was a significant decrease in sexual distress, a significant increase in sexual function in the domains of desire, arousal, lubrication, satisfaction, and orgasm, and a normalization to values within the physiologic range in the following androgens measured: total testosterone, free or bioavAilable testosterone, DHEA, DHEA-S, and androstenedione. Side effects included increased facial hair (11%), weight gain (7%), acne (5%), temporary breast tenderness (1%), loss of head hair (1%) and skin rash (1%). Preliminary results suggest that androgen replacement therapy with dehydroepiandrosterone is a safe and effective treatment for androgen insufficiency and female sexual dysfunction. However, further research is needed, including prospective, multi-institution, placebo-controlled double-blind studies.

Adjuvants, Immunologic↗

PubMedDate not supplied

Effects of medical or surgical castration on erectile function in an animal model.

The goal of this study was to investigate the effects of medical castration (luteinizing hormone-receptor hormone [LH-RH] agonist treatment) or surgical castration on erectile function in an animal model. New Zealand White male rabbits were either kept intact (control); surgically orchiectomized; or treated for 2, 4, or 8 weeks with the LH-RH agonist leuprolide acetate (107 microg/kg/mo). At 2 weeks, plasma testosterone levels of orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of intact control animals, respectively. Erectile function was assessed by continuously recording systemic arterial pressure (SAP) and intracavernosal blood pressure (ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at varying frequencies (2.5-32 Hz). Androgen deprivation by surgical (orchiectomy) or medical (leuprolide acetate) castration reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil (10 microg/kg) did not enhance ICP in surgically orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by surgical or medical castration. Further, Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. These data demonstrate that androgen deprivation achieved by surgical or medical castration adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction.

Animals↗

PubMedDate not supplied

Adipocyte accumulation in penile corpus cavernosum of the orchiectomized rabbit: a potential mechanism for veno-occlusive dysfunction in androgen deficiency.

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.

Adipocytes↗