Effects of castration and testosterone replacement on veno-occlusion during penile erection in the rat.

Aim: To determine if androgens directly regulate veno-occlusion or if androgens act indirectly to maintain the penile structures which control outflow.

Methods: Using CASTRATE and TESTO rats, measurement was made of mean arterial pressure (MAP), intracavernosal pressure (CCP), and intracavernosal flow (CCF) during erection resulting from stimulation of the autonomic innervation of the penis. CCP and CCF were also measured during saline infusion into the cavernosal sinuses before and after treatment with sodium nitroprusside (SNP, a nitric oxide donor drug) to fully relax cavernosal smooth muscle.

Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway.

Relaxation of the smooth muscle cells in the cavernosal arterioles and sinuses results in increased blood flow into the penis, raising corpus cavernosum pressure to culminate in penile erection. Nitric oxide, released from non-adrenergic/non-cholinergic nerves, is considered the principle stimulator of cavernosal smooth muscle relaxation, however, the inhibition of vasoconstrictors (that is, norepinephrine and endothelin-1, refs. 5-9) cannot be ignored as a potential regulator of penile erection.

Receptor-specific influence of endothelin-1 in the erectile response of the rat.

Specific receptor antagonists were used to examine the role of endothelin-1 (ET-1) in the erectile response of the rat. In these studies, intact rats were cannulated to permit the continuous recording of mean arterial pressure (MAP) and intracavernosal pressure (CCP). Erection was induced by electrical stimulation of the autonomic ganglion, which regulates blood flow to the penis.

Androgenic maintenance of the erectile response in the rat.

Ongoing studies in this laboratory have used the castrated rat, with and without testosterone replacement, to investigate how androgens maintain the erectile response. The high intracavernosal pressures during erection depend on both an increase in the rate at which blood flows into the sinuses of the corpus cavernosum and a decrease in the rate at which blood flows out (veno-occlusion). Accordingly, our studies investigated androgenic regulation of the arterioles that regulate inflow and of the intracavernosal muscle that regulates the veno-occlusive mechanism controlling outflow.

Androgenic maintenance of inflow and veno-occlusion during erection in the rat.

Ongoing studies in this laboratory are designed to determine the role of androgens in the maintenance of the erectile response in the rat. Testosterone-treated castrated rats (TESTO) and untreated castrated rats (CASTRATE) were used for measurement of the rate at which blood flows into the cavernous sinuses by timed collections of blood after partial amputation of the penis. A laser Doppler flow meter was employed to determine whether androgens also regulate the veno-occlusive mechanism that controls the rate of blood flow out of the sinuses.

The loss of alpha-adrenergic effect during the erectile response in the long-term diabetic rat.

The present study was designed to investigate the effect of long-term, streptozotocin-induced diabetes on the erectile response in the laboratory rat. Mean arterial blood pressure (MAP) and intracavernosal blood pressure within the erectile tissue (CCP) were continuously monitored during erection elicited by stimulation of the autonomic innervation of the penis. MAP and CCP were also measured during administration of two drugs: nitroglycerin, a nitric oxide donor drug and phenylephrine, an alpha-adrenergic agonist.

Androgenic maintenance of the rat erectile response via a non-nitric-oxide-dependent pathway.

Prior studies have demonstrated that the erectile response in the rat penis is androgen dependent and is mediated by nitric oxide (NO), the neurotransmitter synthesized by the enzyme nitric oxide synthase (NOS). The present studies used L-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, to determine if androgens also regulate alternative pathways leading to the erectile response but not mediated by NO. Castrated rats that were treated with L-NAME (L-NAME CASTRATE) exhibited little or no increase in intracavernosal pressure in response to stimulation of the major pelvic ganglion.

Androgenic regulation of NO availability in rat penile erection.

Prior studies from this laboratory, using untreated castrated (CASTRATE) rats and testosterone-treated castrated (TESTO) rats, have shown that the magnitude of the intracavernosal pressure increase during erection is androgen dependent. Studies from this and other laboratories have also presented evidence suggesting that penile erection is mediated principally by nitric oxide (NO). The present report was designed to confirm that androgens maintain the availability of cavernosal NO and to determine if this androgenic action is exerted at the genomic level modulating the expression of the neuronal form of the nitric oxide synthase gene (nNOS).

Androgens modulate the alpha-adrenergic responsiveness of vascular smooth muscle in the corpus cavernosum.

Rat penile erection is an androgen-dependent process with castration leading to a loss of potency. The present study was designed to determine if one of the mechanisms by which androgens maintain the erectile response is the regulation of the alpha-adrenergic responsiveness of cavernosal smooth muscle. Electrical stimulation of the major pelvic ganglion (MPG) was used to elicit erection in untreated, castrated rats (CASTRATE) or castrated rats given testosterone replacement (TESTO).

Duration of estrogen exposure prior to follicle-stimulating hormone stimulation is critical to granulosa cell growth and differentiation in rats.

Estrogens have been reported to exert both stimulatory and inhibitory effects on granulosa cell function. Previous studies from our laboratory showed that 12 h after administration of diethylstilbestrol (DES; a synthetic estrogen), FSH-stimulated granulosa cell proliferation and aromatase activity were increased; however, 48 h after DES, FSH stimulation of both parameters was inhibited. In other experiments, exposure of rats to DES for a period of 26 h blocked ovulation in response to eCG and hCG administration, whereas the same treatment regimen without DES caused ovulation in all treated rats.

Sites of androgenic regulation of cavernosal blood pressure during penile erection in the rat.

The present studies were designed to determine the role of reactive vascular smooth muscle in the regulation of blood flow into and out of the cavernous sinuses during penile erection in castrated and testosterone-treated animals. While the mean arterial pressure and intracavernosal pressure were continuously monitored, vasoactive drugs were injected into the aorta or into the cavernous sinuses during erection. The results show that both a NO releasing vasodilatory drug and an alpha adrenergic agonist significantly affected both mean arterial pressure and intracavernosal pressure when injected into the aorta.

Effects of castration and androgen replacement on the hemodynamics of penile erection in the rat.

Previous studies from this laboratory have demonstrated that penile erection in the rat is androgen dependent: 1 wk after castration, there was a significant decline in the magnitude of the intracavernosal pressure (CCP) response during erection induced by stimulation of the autonomic ganglion controlling penile blood flow. The response was altered by vasoactive drugs and appeared to involve nitric oxide synthesis. These earlier studies, however, did not identify the site of androgenic action or the mechanism by which the androgens act.

Androgen maintenance of erectile function in the rat penis.

Previous research has shown that the frequency and duration of penile erection is diminished after castration and that replacement with testosterone will restore the process. Using rats, the present study was designed to confirm that erection is androgen-dependent and to determine whether castration and androgen replacement affect the penile vascular smooth muscle responsiveness to vasoactive drugs. Blood pressure in the corpus cavernosum was measured directly during erections induced by electrical stimulation of the autonomic innervation of the penis.

The use of perfused rabbit ovaries to investigate regional ovarian lymphatic flow.

A method is presented for the perfusion of rabbit ovaries in vitro which allows continuous collection of effluent perfusate from the ovarian vein and lymphatic system. The flow of ovarian lymph and the output of progesterone and 20 alpha dihydroprogesterone in lymph and venous effluent from perfused ovaries were measured and the results compared to the same parameters measured in vivo. Rates of flow of lymphatic and venous effluent and lymph/plasma protein ratios measured from perfused ovaries were similar to those measured in vivo, and were not statistically affected by the presence of corpora lutea in the ovaries.

The intraovarian progesterone modulation of follicle development in the rabbit ovary.

Intraovarian progesterone levels were manipulated by surgically adjusting the number of corpora lutea (CL) present in rabbit ovaries and this model was used to study the local effect of luteal progesterone on growth of follicles. The results show that when a single CL or several CL were present, follicle growth was inhibited. However, when all CL on one ovary were removed, increased numbers of follicles grew even when a single CL was present in the contralateral ovary.

The effects of porcine follicular fluid inhibin on gonadotropin secretion in the rabbit.

Porcine follicular fluid (pff), treated with charcoal to remove steroids, was used to determine whether inhibin is active in the laboratory rabbit. When pff (5 ml/4 kg body weight) was injected (ip) into does that had been castrated 2 weeks earlier, there was a significant decline in blood follicle-stimulating hormone (FSH) levels; the decline lasted for 8-12 h. Blood levels of luteinizing hormone (LH) were suppressed, but only briefly at 3 h after injection.