Chapter 6: Functional anatomy of reproductive systems: neuroendocrine systems.
* Review the general organization of the nervous system.
* Describe the gross anatomy of the brain and pituitary gland.
* Describe the anatomic basis for how the brain coordinates reproductive activity.
The reproductive success of an individual is largely determined by its ability to coordinate its reproductive activity with conditions that are favorable for the production and rearing of offspring. For example, it is in the best interest of an animal to avoid reproducing during times of illness, poor nutrition, and extremes in environmental conditions. The nervous system plays a central role in mediating the effects of environment on reproduction. In this chapter we will study the anatomy of the nervous system in relation to its major physiologic functions, which include:
* Detection of stimuli that provide information about the animal's internal and external environments.
* Transmission of information to the brain via neural pathways.
* Integration of neuronal inputs.
* Generation of neural and humoral responses that affect reproductive activity.
Organization of the Nervous System
In order to understand how the nervous system coordinates an animal's reproductive activity with changes in its environment you must have a rudimentary understanding of how the nervous system is structured (Figure 6-1). Anatomically, the nervous system can be divided into the central nervous system, which includes the brain and spinal cord, and the peripheral nervous system, which includes the cranial and spinal nerves (nerves leaving and entering the central nervous system). Functionally, the nervous system can be subdivided based on the direction in which nerve impulses travel and the type of information conveyed by the impulses. With respect to direction of transmission, nerve systems can be classified as afferent (toward the spinal cord and/or brain) or efferent (away from the spinal cord and/or brain). With respect to type of information transmitted, the nervous system can be divided into the somatic system, which deals with the organism's relationship with the external environment (e.g., movement and cognition), and the visceral system, which conveys information about the organism's internal environment (e.g., blood pressure, heart rate, digestion, and so on). The latter is also referred to as the autonomic nervous system. These subdivisions lead to a more elaborate classification scheme--one that includes four types of afferent nerves and two types of efferent nerves. This classification scheme reveals a great deal about the function of the nervous system. Somatic afferent pathways arise from pressure, temperature, and pain receptors in the skin and deeper tissues of the body and send information to the brain and spinal cord via cranial and spinal nerves, respectively. Special somatic pathways originate in the sense organs of the eye and ear and enter the brain via two cranial nerves. Information from receptors in blood vessels, glands, and viscera of the head and body trunk enters the central nervous system via visceral afferent pathways, which include five cranial nerves and all spinal nerves. There are only two major efferent neural pathways. The somatic efferent pathways leave the central nervous system via spinal nerves and innervate various skeletal muscles. The visceral efferent pathways originate in the brain and spinal cord and innervate smooth muscles of viscera and blood vessels, muscles of the heart, and various glands.
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Afferent nerves that enter the brain or spinal cord may synapse with efferent nerves that leave the central nervous system and terminate in various effectors. In addition, afferent neurons may synapse with other afferent nerve cells within the central nervous system. In the spinal cord, these ascending nerve tracts enter various regions of the brain, allowing it to monitor activity of the spinal afferents. Afferent neurons that enter the brain via the cranial nerves may synapse with nerves that innervate other regions of the brain. The brain also has the ability to intervene in the activity of spinal afferents. This is due to descending efferent nerve tracts that synapse with spinal efferent neurons.
Sensory receptors also exist within the brain. The circumventricular organs are chemosensitive cells that are highly innervated with fenestrated capillaries. It is likely that these tissues monitor the chemical composition of blood and respond to changes via neural mechanisms as well as by releasing hormones into the blood and/or cerebrospinal fluid.
In light of the previous discussion, it is appropriate to view the central nervous system as a collection of stimulus-response systems that are orchestrated to regulate the activity of peripheral tissues. The particular characteristics of such systems are described in the next section.
The neural reflex arc is the simplest and most familiar type of stimulus-response system (Figures 6-2a and 6-3). Its components include: 1) a sensory receptor that detects a stimulus (e.g., heat or pressure) and generates a neuronal impulse; 2) a sensory (afferent) neuron that carries an impulse to the spinal cord or brain; 3) a motor (efferent) neuron conveying an impulse away from the spinal cord or brain; 4) an effector (a muscle, gland, and so on), which responds to the efferent impulse. In many cases, an interneuron exists between the afferent and efferent neurons (Figure 6-3).
A second type of stimulus-response system is the neuroendocrine reflex arc (Figure 6-2b). In this case, the efferent neuron is replaced by an endocrine cell, which produces a hormone that induces a response in an effector or target cell. The release of milk by the mammary gland in response to a suckling stimulus is an example of such a reflex. In this case suckling is detected by pressure receptors in the teat and this stimulates afferent pathways that ultimately impinge upon hypothalamic neurosecretory cells that release the hormone oxytocin into the blood. Oxytocin then acts on the alveoli of the mammary gland (the effector) to stimulate milk ejection.
Reproductive activity is also regulated by endocrine reflexes (Figure 6-2c). In this type of reflex, an endocrine cell responds to a stimulus by releasing a hormone into the blood. The hormone then interacts with a target cell to elicit a response. An example of this type of regulatory system is the relationship between blood glucose and the hormone insulin. An increase in circulating levels of glucose stimulates endocrine cells in the pancreas to release insulin, which then acts on several types of target cells to enhance clearance of glucose from the blood. We will discuss such systems in greater detail when we study reproductive endocrinology.
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It is important to keep in mind three important concepts regarding stimulus-response systems. First, it is not uncommon for several of these systems to work together to regulate a particular effector. Second, a particular stimulus-response system may influence several different effectors. Third, two types of efferent responses are possible--stimulatory and inhibitory. These characteristics permit a tight and graded regulation of physiologic processes.
ANATOMY OF THE BRAIN
The stimulus-response systems of the brain regulate a wide array of physiologic functions. Each of the systems described in the previous section plays a role in some aspect of reproduction. An appreciation of how the brain orchestrates these various mechanisms can be gained through studying the structure of this complex organ.
Major Subdivisions of the Brain
Figure 6-4 summarizes the major subdivisions of the brain, the embryonic vesicles that give rise to them, and the adult structures that make up these regions. Each of the major subdivisions in the adult brain consists of neural tissue organized around a central cavity known as a ventricle. Most of our attention is focused on the diencephalon, especially the hypothalamus, a small area that surrounds the third ventricle in the ventral portion of the brain. We are also concerned with the pituitary gland, a bilobed organ that protrudes below the hypothalamus.
Gross Anatomy of the Brain
In order to appreciate the structure and function of the hypothalamus and pituitary gland, it is necessary to review some basic neuroanatomy. Figure 6-5 shows a sagittal view of the sheep's brain. This is a particularly useful perspective because it portrays the anatomic relationship of the hypothalamic-pituitary system to the central nervous system. Note the location of the pituitary gland, which is suspended from the ventral surface of the brain. The hypothalamus is located dorsal to the pituitary gland in the ventral and medial region of the diencephalon, directly beneath the massa intermedia of thalamus. Its rostral limit lies just in front of the optic chiasm. From there it extends bilaterally around the infundibulum (the funnel-shaped stalk from which the pituitary is suspended) and ends caudally at the mammillary body. The third ventricle runs along the median plane of the hypothalamus dividing into left and right halves. It extends from its rostral boundary, the lamina terminalis to the mamillary bodies.
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Circulation of the Brain and Spinal Cord
As with all organs, normal function of the central nervous system requires the delivery of nutrients as well as the transport of wastes away from tissues. The central nervous system is unique in the sense that it relies on two circulatory systems to accomplish these functions: 1) blood flowing through arteries, capillaries, and veins and 2) cerebrospinal fluid flowing through the ventricles and the subarachnoid space (a narrow space lying between the thin layers of connective tissue that encase the central nervous system). Much of the central nervous system is encased by a blood-brain barrier, which prevents blood from circulating through these tissues. The blood-brain barrier is attributed to the predominance of nonfenestrated capillaries that restrict diffusion of solutes into neural tissues. The bulk of tissues that make up the brain and spinal cord are served by cerebrospinal fluid, a cell-free fluid that is produced via ultrafiltration (excluding proteins and other large molecules) of blood plasma. The principle functions of cerebrospinal fluid are to provide chemical buffering capacity to stabilize concentrations of various constituents, transport nutrients and wastes, and provide a medium for neurohormones and neurotransmitters to circulate within the central nervous system.
Figure 6-6 summarizes the circulation of fluid through the central nervous system. Briefly, blood flows to the brain via several arteries. Smaller arteries penetrate the brain and merge with specialized networks of capillaries (chorioid plexus), which line the ventricles. These structures filter blood, resulting in the production of cerebrospinal fluid. The cerebrospinal fluid flows through the ventricular system and then into the subarachnoid space via specialized vents located at the brain stem beneath the caudal portion of the cerebellum. Here, the cerebrospinal fluid becomes the extracellular fluid supplying the bulk of tissue in the central nervous system. This fluid is returned to the blood via specialized organs (arachnoid granulations), which protrude into the venous sinuses of the brain. These sinuses comprise the venous system that carries blood away from the brain and into the jugular veins, which then return blood to the heart.
Several areas adjacent to the cerebral ventricles are not protected by the blood-brain barrier. In these circumventricular organs (Figure 6-7), blood from the arteries supplying the brain enters capillary networks consisting of fenestrated capillaries and then returns to the venous circulation via the venous sinuses. These organs arise from the lining of the ventricles and are comprised of chemosensitive nerve cells (chemoreceptors), which secrete various substances into the surrounding vasculature and/or ventricles. Circumventricular organs surrounding the third ventricle include the subfornical organ, sub-commissural organ, organum vasculosum of the lamina terminalis, pineal gland, posterior pituitary gland, and part of the median eminence. The area postrema is located in the roof of the fourth ventricle. Several of these structures play important roles in regulating reproductive activity in mammals.
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ANATOMY OF THE HYPOTHALAMIC-PITUITARY AXIS
The hypothalamus and pituitary gland are intimately associated in both anatomic and functional ways. Figure 6-8 shows an expanded view of the hypothalamic-pituitary interface. The ventral portion of the hypothalamus forms a mound (median eminence) that is continuous with the infundibulum (stalk), which connects with and supports the pituitary gland.
Anatomy of the Pituitary Gland
The hypothalamic-pituitary unit is located deep within the skull in the ventral cranial cavity (Figure 6-9). The pituitary gland is embedded in the sella turcica (Turkish saddle), a prominence in the dorsal surface of the sphenoid bone forming portions of the sides and base of the skull near the orbits (eye sockets). In four-legged animals, the infundibular stalk angles caudally, so that the pituitary gland lies in a ventral and caudal position relative to the hypothalamus. In primates, the pituitary lies directly beneath the hypothalamus.
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The pituitary gland (also known as the hypophysis) consists of two major parts (lobes), which are derived from different embryonic tissues (Figure 6-10). The posterior lobe (neurohypophysis or pars nervosa) is derived from the brain, whereas the adenohypophysis (or pars distalis) develops from the oral ectoderm (epithelium forming the roof of the mouth) of the embryo. In many species the adenohypophysis can be further subdivided into a large anterior portion and a smaller intermediate lobe (or pars intermedia). Some species lack a distinct intermediate lobe.
Functional and Structural Relationships between Hypothalamus and Pituitary Gland
Blood is supplied to the pituitary gland by branches of the arteries that surround the base of the infundibulum (Figure 6-11). The superior hypophysial artery enters at the interface between the ventral hypothalamus and infundibulum and supplies the anterior pituitary gland. The inferior hypophysial artery enters the ventral region of the posterior pituitary gland. Each of the lobes is drained by hypophysial veins.
The vasculatures of the anterior and posterior lobes of the pituitary gland are remarkably different and reflect differences in the anatomic and physiologic relationships with the hypothalamus (Figure 6-12). In the posterior lobe, blood from the inferior hypophysial artery flows into a capillary plexus, which supplies blood to surrounding tissues. The posterior pituitary gland is made up predominantly of neural tissue; in particular the axons of neurons, which originate in the hypothalamus and terminate near the capillaries. Blood draining from these capillaries can flow in two directions. Much of the blood flows into the hypophysial vein, which carries blood to the jugular vein. Some blood enters so-called short portal vessels, which are sinusoidal vessels that converge on a capillary bed in the anterior pituitary gland.
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In contrast to the posterior pituitary gland, the anterior pituitary gland receives only a little blood directly from arteries. The bulk of blood flowing into the anterior pituitary gland arrives via a portal vascular system. The superior hypophysial artery feeds into a capillary plexus that is located in the median eminence of the hypothalamus. Neurons from the hypothalamus terminate on the median eminence capillaries. This capillary plexus is sometimes referred to as the primary capillary plexus. These capillaries drain into "long portal blood vessels" that run longitudinally along the infundibular stalk and drain into a secondary capillary plexus in the anterior lobe of the pituitary gland. The capillaries of this region drain into a hypophysial vein.
Having described the circulation of the pituitary gland, it is now possible to explain how the hypothalamus communicates with the anterior and posterior lobes of this important organ (Figure 6-13). Communication between the hypothalamus and posterior lobe is primarily neuronal. Two peptides (oxytocin and vasopressin) are produced in the cell bodies of neurons located in the hypothalamus, and are transported to axon terminals that lie adjacent to capillaries. Stimulation of these neurons causes the peptides to be released into the surrounding extracellular space. Because the posterior lobe lies outside the blood-brain barrier (contains fenestrated capillaries), the peptides can diffuse into the capillaries and enter the general circulation. Alternatively, these neurohormones can enter the anterior pituitary gland via the short portal vessels.
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Communication between the hypothalamus and anterior lobe occurs through neurovasculature connections. The capillaries of the median eminence are fenestrated. Therefore, the secretory products of hypothalamic neurons that impinge upon the primary capillary plexus enter the blood and are carried via the portal vessels to the secondary capillary plexus. These chemicals diffuse out of the capillaries and stimulate or inhibit release of hormones by endocrine cells located in the anterior lobe. These pituitary hormones diffuse into the secondary capillary plexus and enter the general circulation through the hypophysial vein.
BOX 6-1 Focus on Fertility: Discovery of the Hypothalamic-Hypophysial Portal System One of the major problems with textbooks is that they often take too much for granted. For example, the idea that the release of hormones from the anterior pituitary gland is regulated by various hypothalamic hormones is one of the fundamental assumptions underlying reproductive physiology. How did we come to accept this hypothesis? The elaborate arrangement of the portal blood vessels found along the pituitary stalk was described in detail during the 1930s. However, a full appreciation of its functional importance was not attained until the 1970s. Although the arrangement of blood vessels connecting the hypothalamus and anterior pituitary gland were recognized as portal in nature (i.e., running between two capillary plexes), early investigators erroneously concluded that the direction of blood flow was upward from the pituitary gland toward the hypothalamus. However, several subsequent avenues of research soon challenged this conclusion. First, a study in the 1930s showed that surgical transection of the infundibular stalk in toads caused necrosis of the anterior pituitary. It was therefore suggested that blood flowed in a downward direction from the hypothalamus to the pituitary gland. Studies in mammals followed and confirmed this conclusion. Second, in the 1940s and 1950s several investigators documented this downward flow of blood by directly observing blood flow in portal vessels of rats, mice, dogs, cats and monkeys. Finally, direct evidence supporting this view came from an elegant experiment done with rats in the early 1970s. When dyes were injected into individual portal vessels they eventually infiltrated the tissue of the anterior pituitary gland. From the moment investigators embraced the idea of a downward movement of blood within the portal vessels, there was growing support for the hypothesis that the hypothalamus regulated the anterior pituitary gland via humoral (blood-borne) factors. A series of classic endocrine experiments generated empirical support for this hypothesis. As noted earlier, disruption of the portal vascular system causes deterioration of anterior pituitary tissue. The idea that the hypothalamus is the source of humoral factors that support the functions of anterior pituitary cells came from the fact that grafts of anterior pituitary tissues remained functional when transplanted to the median eminence, but not when transplanted to other regions of the brain (e.g., temporal lobe of cerebrum) or in the highly vascularized renal capsule. At the time of these studies it was becoming clear that the anterior pituitary gland regulated gonadal function via two gonadotropins. Work concerning the vascular relationship between the hypothalamus and pituitary gland gave rise to the idea that a hypothalamic gonadotropin-releasing factor regulates secretion of LH and FSH. Support for this hypothesis came from experiments that showed that surgical disconnection of the portal vascular system, or placement of an impermeable barrier between the hypothalamus and pituitary gland resulted in decreased production of LH and FSH by the pituitary gland as well as infertility. By the 1970s the structure of this factor was determined and became known as gonadotropin-releasing hormone (GnRH). Today, this and other hypothalamic hormones are produced synthetically and are used clinically to treat a variety of endocrine disorders including infertility.
Organization of the Hypothalamus
The hypothalamus is an organ of integration. It receives diverse neural inputs from the peripheral and central nervous systems as well as blood-borne signals. All of these signals converge on the hypothalamus and are blended to generate humoral signals that regulate the pituitary gland. The tissue of the hypothalamus consists primarily of nuclei and nerve tracts (see Figure 6-13). The hypothalamic nuclei appear as bundles of neuron cell bodies arranged in bilateral pairs along the walls of the third ventricle. Only a few of these play a role in reproduction. The others control other autonomic functions as well as release of pituitary hormones that regulate systems other than the reproductive system. Large cell bodies (magnocellular) localized in the paraventricular nuclei and supraoptic nuclei produce the hormone oxytocin, which plays a role in milk ejection, parturition, and regulation of the ovary. The axons of these cells course ventrally and caudally into the infundibulum and terminate in the posterior pituitary gland. This nerve tract is called the tuberohypophysial tract. The medial preoptic nuclei, located in the anterior hypothalamus, play a role in sexual behavior. A hypothalamic hormone called gonadotropin-releasing hormone (GnRH) controls the release of two pituitary hormones (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) that regulate gonadal function. Neurons that produce GnRH are not localized in particular nuclei or discrete regions of the brain (Figure 6-14). They are scattered sparsely throughout the forebrain from the olfactory bulbs, rostrally, to the hypothalamus, caudally. Within the hypothalamus, cell bodies of GnRH neurons are found in the medial preoptic area, anterior hypothalamic area, and medial basal hypothalamus. The majority of this type of cell body is found in the medial preoptic area. Axons from these cells course laterally and caudally and finally terminate in the median eminence, forming the tuberoinfundibular tract. Neurosecretory cells from other locations in the hypothalamus (e.g., ventral region) also send axons toward the median eminence and contribute to this tract. The products of these neurons regulate release of adenohypophysial hormones other than those regulating reproduction.
The neurons that produce oxytocin and GnRH, as well as those producing other hypothalamic hormones, are regulated by neurons that originate in regions of the brain outside the hypothalamus. It is beyond the scope of our discussion to describe these neuro-pathways in any detail. For our purposes it is sufficient to understand only that neurons from these regions synapse with hypothalamic neurons and communicate with them via various neurotransmitters.
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SUMMARY OF MAJOR CONCEPTS
* With respect to reproduction, the brain plays a central role in timing reproductive activity with favorable environmental conditions.
* The brain regulates bodily functions, including reproduction, via various stimulus-response systems that involve neuronal and humoral mechanisms.
* A small portion of the diencephalon, the hypothalamus, integrates neuronal and humoral inputs and regulates reproductive activity via regulation of the pituitary gland.
* Most of the central nervous system is protected by a blood-brain barrier, meaning that only some blood constituents enter the extracellular fluid of the brain (cerebrospinal fluid).
* The pituitary gland consists of two major lobes, each of which plays a role in reproduction. The anterior lobe interacts with the hypothalamus through a neurovascular connection whereas the posterior lobe is connected to the hypothalamus by a neuronal system.
1. When male mammals encounter sexually receptive females, they express particular sexual behaviors (e.g., investigation, mounting, erection of the penis, ejaculation). Outline a stimulus response system that explains how the male behavior is generated.
2. Suppose you take simultaneous blood samples from a carotid artery and a jugular vein and measure the concentration of LH in each sample. Which sample would you expect to have the greater concentration of LH? Why?
3. Scientists have discovered several peptide hormones that are produced in various peripheral tissues, but affect appetite, which is regulated by the central nervous system (specifically, the hypothalamus). It is unlikely that these large molecules can pass the blood-brain barrier. If so, then how can these blood-borne signals affect activity of the central nervous system? Where might these peptides act?
4. In rare occasions, human infants as young as one year of age undergo precocious puberty; that is, they display adult secondary sex traits. One of the major causes of this anomaly is a tumor in the medial-basal hypothalamus. Explain how such a tumor might cause this. (Hint: Recall that secondary sex traits develop in response to production of high levels of gonadal hormones).
Carpenter, M.B. 1976. Human Neuroanatomy (Seventh Edition). Baltimore: Williams and Wilkins.
Dyce, K.M., W.O. Sack and C.J.G. Wensing. 2002. Textbook of Veterinary Anatomy, Third Edition. Philadelphia: Saunders.
Evans, H.E. and G.C. Christensen. 1979. Miller's Anatomy of the Dog, Second Edition. Philadelphia: W.B. Saunders Company.
Everett, J.W. 1994. Pituitary and Hypothalamus: Perspectives and Overview. In: E. Knobil and J.D. Neill, The Physiology of Reproduction Vol. 2., Second Edition. New York: Raven Press, pp. 1509-1526.
Keith K. Schillo, PhD
Department of Animal and Food Sciences
University of Kentucky
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|Author:||Schillo, Keith K.|
|Publication:||Reproductive Physiology of Mammals, From Farm to Field and Beyond|
|Date:||Jan 1, 2009|
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