Sex steroids influence the central nervous system, even in utero, and play important roles in determining and regulating complex patterns of sexual behavior. However, reproductive behavior is extraordinarily complex and is influenced by numerous factors other than sex steroids, such as one's genetic constitution, social contacts, and the age at which hormones exert their effects. In this subchapter we describe the neurophysiology of the male sex act.
The sympathetic and parasympathetic divisions of the autonomic nervous system control the male genital system
The testes, epididymis, male accessory glands, and erectile tissue of the penis (corpora cavernosa and corpus spongiosum) receive dual innervation from the sympathetic and parasympathetic branches of the autonomic nervous system (ANS; see pp. 340–341). The penis also receives both somatic efferent (i.e., motor) and afferent (i.e., sensory) innervation via the pudendal nerve (S2 through S4).
Sympathetic Division of the ANS
As described in Chapter 14, the preganglionic sympathetic neurons originate in the thoracolumbar segments of the spinal cord (T1 through T12, L1 through L3; see Fig. 14-4). For the lower portion of the sympathetic chain (T5 and below), the preganglionic fibers may pass through the paravertebral sympathetic trunk and then pass via splanchnic nerves to a series of prevertebral plexuses and ganglia (see below). Once within one of these plexuses or ganglia, the preganglionic fiber may either (1) synapse with the postganglionic fiber, or (2) pass on to a more caudal plexus or ganglion without synapsing.
The sympathetic efferent (motor) nerve fibers that are supplied to the male sex organs emanate from five primary prevertebral nerve plexuses (Fig. 54-10): the celiac, superior mesenteric, inferior mesenteric, superior hypogastric, and inferior hypogastric or pelvic plexuses. The celiac plexus is of interest in a discussion of male sex organs only because preganglionic sympathetic fibers pass through this plexus on their way to more caudal plexuses. The superior mesenteric plexus lies on the ventral aspect of the aorta. Preganglionic fibers from the celiac plexus pass through the superior mesenteric plexus on their way to more caudal plexuses.
FIGURE 54-10 Innervation of the male genital system. A, The sympathetic innervation of the male genital system involves a series of prevertebral nerve plexuses and ganglia. B, Three motor pathways as well as a sensory pathway are involved in erection. (1) Parasympathetic innervation: Preganglionic parasympathetic fibers arise from the sacral spinal cord and from the pelvic nerve, and they synapse in the pelvic plexus. The postganglionic parasympathetic fibers follow the cavernous nerve to the penile corpora and vasculature. (2) Sympathetic innervation: Preganglionic sympathetic fibers exit the thoracolumbar cord and synapse in one of several prevertebral ganglia. Postganglionic fibers reach the genitalia via the hypogastric nerve, the pelvic plexus, and the cavernous nerves. (3) Somatic innervation: Somatic (i.e., not autonomic) motor fibers originate in the sacral spinal cord, forming the motor branch of the pudendal nerve. The fibers innervate the striated penile muscles. In addition to these three motor pathways, there is also an afferent pathway from the penis. The dorsal nerve of the penis is the main terminus of the sensory pudendal nerve and is the sole identifiable root for tactile sensory information from the penis.
Most of the preganglionic sympathetic fibers pass from the superior mesenteric plexus to the inferior mesenteric plexus, although some of the nerves pass directly to the hypogastric plexus. The superior hypogastric plexus is a network of nerves located distal to the bifurcation of the aorta. The inferior hypogastric or pelvic plexus receives sympathetic supply from the hypogastric nerve.
In addition to these five plexuses, two other small ganglia are of interest. The spermatic ganglion is located near the origin of the testicular artery from the aorta. The spermatic ganglion receives fibers directly from the lumbar sympathetic nerves and from branches of several other ganglia. The hypogastric (or pelvic) ganglion is located at the junction of the hypogastric and pelvic nerve trunks.
Parasympathetic Division of the ANS
The preganglionic parasympathetic neurons relating to the male reproductive system originate in the sacral segments of the spinal cord (S2 through S4; see Fig. 14-4). These fibers pass via the pelvic nerve to the pelvic plexus, where they synapse with the postganglionic parasympathetic neurons.
Sensory fibers are present in all the nerve tracts described (see Fig. 14-2). These fibers either (1) travel with the pelvic nerves to the dorsal root of the spinal cord, (2) travel with the sacral nerves to the sympathetic trunk and then rise in the sympathetic trunk to the spinal cord, or (3) travel with the hypogastric nerve and ascend to more rostral prevertebral plexuses and then to the spinal cord.
The principal functions of motor innervation to the male accessory glands include control of smooth-muscle contraction, vascular tone, and epithelial secretory activity.
Erection is primarily under parasympathetic control
During erection, relaxation of the smooth muscles of the corpora cavernosa and the corpus spongiosum allows increased inflow of blood to fill the corporal interstices and results in an increase in volume and rigidity. Vascular actions of the smooth muscles of the corpora and the perineal striated muscles are coordinated. For example, contraction of the striated muscles overlying the vascular reservoirs of the penile bulb increases the pressure of the blood in the corpora and promotes increased rigidity. N54-10 The three major efferent (i.e., motor) pathways for the regulation of penile erection are parasympathetic (pelvic nerve), sympathetic (hypogastric nerve), and somatic (pudendal nerve). The two corpora cavernosa and the corpus spongiosum are usually coordinated in their erection (i.e., tumescence) and detumescence. However, they may act independently inasmuch as their vascular and neuroeffector systems are relatively independent.
Nonvascular Contributions to Erection
Contributed by Ervin Jones
Striated muscle also contributes to erection. The contribution of skeletal muscle varies among species but plays a lesser role in humans, where erections are purely vascular.
The first and most important pathway for erection is the parasympathetic division of the ANS. These fibers derive from the lumbar and sacral portions of the spinal cord and travel via the pelvic nerve, the pelvic plexus, and the cavernous nerve to the penile corpora and vasculature (see Fig. 54-10). This pathway is almost entirely parasympathetic but apparently also carries some sympathetic fibers (see below). The parasympathetic activity results in vasodilatation of the penile blood vessels, which increases blood flow to the cavernous tissue and engorges the organ with blood. In erectile tissue, parasympathetic postganglionic terminals release acetylcholine (ACh) and nitric oxide (NO), similar to the system discussed in Figure 14-11. First, ACh binds to M3 muscarinic receptors on endothelial cells. Via Gαq, these receptors would then lead to stimulation of PLC, increased [Ca2+]i, activation of NO synthase, and local release of NO (see p. 66). Second, the nerve terminals may also directly release NO. Regardless of the source of NO, this gas diffuses to the vascular smooth-muscle cell, where it stimulates guanylyl cyclase to generate cGMP, which in turn causes vasodilation (see Table 20-8; Box 54-3).
Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) are reasonably well tolerated oral medications used to treat erectile dysfunction. Men with erectile dysfunction experience significant improvement in rigidity and duration of erections after treatment with these medications.
As indicated in the text, the smooth-muscle tone of the human corpus cavernosum is regulated by the synthesis and release of NO, which raises [cGMP]i in vascular smooth-muscle cells, thereby relaxing the smooth muscle and leading to vasodilatation and erection. Breakdown of cGMP by cGMP-specific phosphodiesterase type 5 limits the degree of vasodilation and, in the case of the penis, limits erection. Sildenafil, vardenafil, and tadalafil are highly selective high-affinity inhibitors of cGMP-specific phosphodiesterase type 5 and thereby raise [cGMP]i in smooth muscle and improve erection in men with erectile dysfunction.
The new medications are attractive because they are effective and benefit most men with insufficient erection. These medications stimulate erection only during sexual arousal and thus have a rather natural effect. They can be taken as little as 1 hour before planned sexual activity.
One of the side effects of sildenafil is “blue vision,” a consequence of the effect of inhibiting cGMP-specific phosphodiesterase in the retina. In individuals taking other vasodilators, sildenafil can lead to sudden death. In women, sildenafil may improve sexual function by increasing blood flow to the accessory secretory glands (see pp. 1108 and 1127).
The second pathway, which is thought to be entirely sympathetic, exits the thoracolumbar spinal cord. The preganglionic fibers then course via the least splanchnic nerve, the sympathetic chain, and the inferior mesenteric ganglion. The postganglionic fibers reach the genitalia via the hypogastric nerve, the pelvic plexus, and the cavernous nerves (see above). Tonic sympathetic activity contributes to penile flaccidity. During erection, a decrease in this sympathetic tone allows relaxation of the corpora and thus contributes to tumescence.
The third pathway is the motor branch of the pudendal nerve. It has primarily somatic (i.e., not autonomic) fibers, originates in the sacral spinal cord, and innervates the striated penile muscles. Contraction of the striated ischiocavernosus muscle during the final phase of erection increases pressure inside the corpora cavernosa to values that are even higher than systemic arterial pressure. Contraction of the striated bulbospongiosus muscle increases engorgement of the corpus spongiosum, and thus the glans penis, by pumping blood up from the penile bulb underlying this muscle. Humans are apparently less dependent on their striated penile muscle for achieving and maintaining erection. However, these muscles are active during ejaculation and contribute to the force of seminal expulsion.
Postganglionic neurons release other so-called nonadrenergic, noncholinergic neurotransmitters (see p. 543)—including NO—that also contribute to the erectile process.
The penis also has an afferent pathway. The dorsal nerve of the penis is the main terminus of the sensory pudendal nerve and is the sole identifiable root for tactile sensory information from the penis.
Emission is primarily under sympathetic control
The term seminal emission refers to movement of the ejaculate into the prostatic or proximal part of the urethra. Under some conditions, seminal fluid escapes episodically or continuously from the penile urethra; this action is also referred to as emission. Emission is the result of peristaltic contractions of the ampullary portion of the vas deferens, the seminal vesicles, and the prostatic smooth muscles. These actions are accompanied by constriction of the internal sphincter of the bladder, which is under sympathetic control (see p. 736); this constriction of the sphincter prevents retrograde ejaculation of sperm into the urinary bladder (see Box 54-3).
The rhythmic contractions involved in emission result from contraction of smooth muscle. In contrast to those of other visceral organ systems, the smooth-muscle cells of the male ducts and accessory glands fail to establish close contact with one another and show limited electrotonic coupling. In the male accessory glands, individual smooth-muscle cells are directly innervated and have only limited spontaneous activity (i.e., multiunit smooth muscle; see p. 243). This combination allows a fast, powerful, and coordinated response to neural stimulation.
Motor Activity of the Duct System
A gradation between two forms of smooth-muscle activity occurs along the male duct system. The efferent ducts and proximal regions of the epididymis are sparsely innervated but display spontaneous contractions that can be increased via adrenergic agents acting on α-adrenergic receptors. In contrast, the distal end of the epididymis and the vas deferens are normally quiescent until neural stimulation is received during the ejaculatory process. Contraction of the smooth muscle of the distal epididymis, vas deferens, and accessory sex glands occurs in response to stimulation of the sympathetic fibers in the hypogastric nerve and release of norepinephrine. Indeed, an intravenous injection of epinephrine or norepinephrine can induce seminal emission, whereas selective chemical sympathectomy or an adrenergic antagonist can inhibit seminal emission. The role of parasympathetic innervation of the musculature of these ducts and accessory glands in the male is not entirely clear. Parasympathetic fibers may be preferentially involved in basal muscular activity during erection (i.e., before ejaculation) and during urination.
Secretory Activity of the Accessory Glands
The effect of autonomic innervation on the secretory activity of the epithelia of the male accessory glands has been studied extensively. Electrical stimulation of the pelvic nerves (parasympathetic) induces copious secretions. The secretory rate depends on the frequency of stimulation and can be blocked with atropine, a competitive inhibitor of muscarinic ACh receptors. Cholinergic drugs induce the formation of copious amounts of secretions when these drugs are administered systemically. Secretions from the bulbourethral glands also contribute to the ejaculate. The bulbourethral glands do not store secretions but produce them during coitus. The secretory activity of the bulbourethral glands also appears to be under cholinergic control inasmuch as administration of atropine causes marked inhibition of secretion from these glands.
Control of the motor activity of the ducts and the secretory activity of the accessory glands is complex and involves both the sympathetic and the parasympathetic divisions of the ANS. The central nervous system initiates and coordinates all these activities (Box 54-4).
As noted in the text, emission is normally accompanied by constriction of the internal urethral sphincter. Retrograde ejaculation occurs when this sphincter fails to constrict. As a result, the semen enters the urinary bladder rather than passing down the urethra. Retrograde ejaculation should be suspected in patients who report absent or small-volume ejaculation after orgasm. The presence of >15 sperm per high-power field in urine specimens obtained after ejaculation confirms the occurrence of retrograde ejaculation.
Lack of emission or retrograde ejaculation may result from any process that interferes with innervation of the vas deferens and bladder neck. Several medical illnesses, such as diabetes mellitus (which can cause peripheral neuropathy) and multiple sclerosis, or the use of pharmaceutical agents that interfere with sympathetic tone can lead to retrograde ejaculation. Retrograde ejaculation may also occur as a result of nerve damage associated with certain surgical procedures, including bladder neck surgery, transurethral resection of the prostate, colorectal surgery, and retroperitoneal lymph node dissection. Retrograde ejaculation from causes other than surgery involving the bladder neck may be treated with pharmacological therapy. Sympathomimetic drugs such as phentolamine (an α-adrenergic agonist), ephedrine (which enhances norepinephrine release), and imipramine (which inhibits norepinephrine reuptake by presynaptic terminals) may promote normal (i.e., anterograde) ejaculation by increasing the tone of the vas deferens (propelling the seminal fluid) and the internal sphincter (preventing retrograde movement).
Ejaculation is under the control of a spinal reflex
As discussed, seminal emission transports semen to the proximal (posterior) part of the urethra. Ejaculation is the forceful expulsion of this semen from the urethra. Ejaculation is normally a reflex reaction triggered by the entry of semen from the prostatic urethra into the bulbous urethra. Thus, emission sets the stage for ejaculation. The ejaculatory process is a spinal cord reflex, although it is also under considerable cerebral control. The afferent (i.e., sensory) impulses reach the sacral spinal cord (S2 through S4) and trigger efferent activity in the somatic motor neurons that travel via the pudendal nerve. The resulting rhythmic contractions of the striated muscles of the perineal area—including the muscles of the pelvic floor, as well as the ischiocavernosus and bulbospongiosus muscles—forcefully propel the semen via the urethra through the external meatus. In addition, spasmodic contractions of the muscles of the hips and the anal sphincter generally accompany ejaculation.
Orgasm is a term best restricted to the culmination of sexual excitation, as generally applied to both men and women. Orgasm is the cognitive correlation of ejaculation in the human male. Although orgasm, the pleasurable sensation that accompanies ejaculation, is not well understood, clearly it is as much a central phenomenon as it is a peripheral one. N54-11
Neuronal Lesions Affecting Erection and Ejaculation
Contributed by Ervin Jones
Erectile dysfunction is often associated with disorders of the central and peripheral nervous systems. Spinal cord disease and peripheral neuropathies are of particular interest, and effects of spinal cord injuries have been studied in some detail. Erectile capacity is usually preserved in men with lesions of the premotor neurons (neurons that project from the brain to the spinal cord; eTable 54-1). In these men, reflexogenic erections occur in 90% to 100% of cases, whereas psychogenic erections do not occur because the pathways from the brain are blocked. Ejaculation is more significantly impaired with upper than with lower motor neuron lesions, presumably because of loss of the psychogenic component.
A clinically important feature of the spinal segmentation of nerve roots (i.e., thoracolumbar and lumbosacral) for generation of erection is that spinal or peripheral nerve damage may affect only one of the effector systems. Because the lumbosacral system also carries most of the penile afferents, erection in response to penile stimulation (reflexogenic) is most affected by damage to the lower spinal cord or the nerves that project there. Evidence from men with spinal injuries in the T10 through T12 region has implicated the sympathetic thoracolumbar pathway in mediation of erections resulting from sexual stimuli received via the cranial nerves or generated within the brain as memories, fantasies, or dreams. In men with lower motor neuron lesions, reflexogenic erections are absent. However, psychogenic erections still occur in most men with incomplete lesions and in about one fourth of men with complete lesions. It remains uncertain whether this sympathetic pathway is normally the principal route for psychogenic erections or whether it just assumes the role when lumbosacral parasympathetic pathways are damaged.
Effects of Neural Lesions on Erection and Ejaculation
EFFECT ON EJACULATION
Upper motor neuron
Lower motor neuron