BASIC CONCEPTS OF NEURAL AND ENDOCRINE REGULATION [ Academic Script ] Course : Zoology Name : B.Sc. 2nd Year Paper No. : Z-203B & Title : Vertebrate Endocrinology And Reproductive Biology Topic No. : 1 & Title : Integrative Physiology Basic concepts of neural and endocrine regulation of physiological processes. Lecture : Integrative Physiology &Title : Basic Concepts of Neural and Endocrine Regulation of physiological processes
INTRODUCTION We know different physiological processes, metabolism etc.in animals. Each physiological process requires control and coordination. All functional components necessary to be controlled are put together so that they work consistently. Thus, coordination is the process through which two or more organs interact and complement the functions of each other. For example, when we do physical exercise, we notice an increase in the rate of breathing, heartbeat, flow of blood etc. When we stop physical exercise, we observe that breathing, heartbeat, blood flow etc. gradually return to normal. Thus during physical exercise, the activity of various organs of body are coordinated, controlled and integrated jointly by two systems : the nervous system and the endocrine system. In humans all the physiological activities are controlled and coordinated by nervous and endocrine systems. The nervous system provides an organised network of nerves for fast coordination and the endocrine system provides chemical integration through hormones. Endocrine system relies on the production and release of hormones from various glands and on the transport of those hormones via the bloodstream. Thus, the two communication systems complement each other. In addition, both systems interact: Stimuli from the nervous system can influence the release of certain hormones and vice versa. NEUROENDOCRINE INTERACTIONS Together with the nervous and circulatory systems, the endocrine system is critical for the integration and coordination of various bodily
functions. Not only is the endocrine system conceptually related to the other two systems but the function of the endocrine system in homeostatic maintenance of the body would be impossible without its functional integration with the central nervous system and circulatory system. The role of the circulatory system in endocrine function is contained in the definition of hormone as a signaling chemical that uses the blood circulation to reach the target tissues. The CNS, on the other hand, has a more active role in endocrine function as the CNS is directly involved in synthesis and release of some hormones (e.g. oxytocin) and it is directly involved in regulating the function of majority of endocrine glands. The primary interface between the CNS and the endocrine system is the hypothalamus, which is at the same time an integral part of the central nervous system and an endocrine gland. Via the pituitary gland the hypothalamus controls the function of the peripheral endocrine glands such as adrenal and thyroid glands. All endocrine glands are innervated by autonomic nerves and these may either directly control their endocrine function and/or regulate blood flow within the gland. Hormones, in turn, may affect central nervous system functions such as mood, anxiety and behavior. Neurosecretory cells may directly convert a neural signal into a hormonal signal. In other words they act as transducers converting electrical energy into chemical energy. Thus, activation of neurosecretory cells leads to secretion of a hormone into the circulation. These neurosecretory cells include: those that secrete hypothalamic releasing and inhibiting hormones controlling TSH, ACTH, PRL,LH and FSH release from the anterior pituitary gland; the hypothalamic neurons (the axon terminals of) which secrete oxytocin and vasopressin from the posterior pituitary gland; the chromaffin cells of the adrenal medulla (embryologically modified neurons) that
secrete epinephrine and norepinephrine into the general circulation. The significance of these neurosecretory cells is that they allow the endocrine system to integrate and respond to changes in the external environment. Thus, for example, the CRH-ACTH-cortisol axis can be activated by stress generated from external cues as is oxytocin secretion by a suckling baby. HYPOTHALAMUS The hypothalamus makes up part of the diencephalon of the brain and is situated below the thalamus where it forms the floor of the third ventricle. Directly below the hypothalamus lies the pituitary gland. The two areas are connected by neuronal tissue and blood vessels within the infundibular stalk. Hypothalamus controls many bodily functions, including eating and drinking, sexual functions and behaviors, blood pressure and heart rate, body temperature maintenance, the sleepwake cycle, and emotional states (e.g., fear, pain, anger, and pleasure). Hypothalamic hormones play pivotal roles in the regulation of many of those functions. Because the hypothalamus is part of the central nervous system, the hypothalamic hormones actually are produced by nerve cells (i.e., neurons). In addition, because signals from other neurons can modulate the release of hypothalamic hormones, the hypothalamus serves as the major link between the nervous and endocrine systems. For example, the hypothalamus receives information from higher brain centers that respond to various environmental signals. Consequently, hypothalamic function is influenced by both the external and internal environments as well as by hormone feedback. Stimuli from the external environment that indirectly influence hypothalamic function include the light-dark cycle; temperature; signals from other members of the same species; and a wide variety of visual, auditory, olfactory, and sensory stimuli. The communication between other brain areas and the hypothalamus,
which conveys information about the internal environment, involves electrochemical signal transmission through molecules called neurotransmitters (e.g., aspartate, dopamine,, glutamate, norepinephrine, and serotonin). The complex interplay of the actions of various neurotransmitters regulates the production and release of hormones from the hypothalamus. The hypothalamus itself acts as an endocrine organ. Hypothalamic neurons synthesize hormones, transport them along axons within the infundibulum, and release them into the circulation at the posterior lobe of the pituitary gland. The hypothalamic hormones are released into blood vessels that connect the hypothalamus and the pituitary gland (i.e., the hypothalamic hypophyseal portal system). Because they generally promote or inhibit the release of hormones from the pituitary gland, hypothalamic hormones are commonly called releasing or inhibiting hormones. Releasing hormones (RH) stimulate the synthesis and secretion of one or more hormones at the anterior lobe. Inhibiting hormones (IH) prevent the synthesis and secretion of hormones from the anterior lobe. The rate at which the hypothalamus secretes regulatory hormones is controlled by negative feedback. The major releasing and inhibiting hormones include the following TRH - Thyrotropin Releasing Hormone This hormone will affect the anterior pituitary which will then affect thyroid gland activity PRH - Prolactin Releasing Hormone and PIH-- Prolactin Release- Inhibiting Hormone. These two hormones will affect the secretion of
prolactin from the anterior pituitary CRH - Corticotropin Releasing Hormone This hormone affects ACTH release from the anterior pituitary GnRH - Gonadotropin Releasing Hormone This hormone will affect the anterior pituitary which will then affect the gonadal release of sex hormones GHRH - Growth Hormone Releasing Hormone and SS Somatostatin or GHIH for growth hormone release-inhibiting hormone. These two hormones both affect secretion of growth hormone by the anterior pituitary. MRH/MRIH - These two hormones regulate MSH from anterior pituitary. Besides this the hypothalamus makes two additional hormones: OT (oxytocin) and ADH (antidiuretic hormone) or vasopressin. The hypothalamus does NOT secrete these hormones, however. Instead, the neurons that make the hormones transport the hormones to their axonal terminals. These axonal terminals are located in the posterior pituitary. The hypothalamus serves as the integrating center for interoceptive (originating within the CNS) and exteroceptive (originating outside the CNS) stimuli. This diverse collection of nuclei at the base of the brain processes the stimuli and generates appropriate responses. These responses are mediated in large part by the neuroendocrine and endocrine signals originating along the hypothalamo-pituitary axis. For example, if a person finds him/her self dehydrated in the desert, the hypothalamus senses the increase in osmotic strength of the extracellular fluids. In parallel, the loss of extracellular volume is
sensed by the peripheral nervous system and this information is also relayed to the hypothalamus. These stimuli result in a number of different responses, including the release of ADH in the posterior pituitary which will preserve the water in kidneys and stimulate thirst. An additional hypothalamic response in this situation might be release of CRH in response to stress. CRH will target the anterior pituitary to release ACTH and subsequently release glucocorticoids from the adrenal gland. In order to understand themechanisms by which the hypothalamus and pituitary gland communicate to accomplish these effects, we need to understand the organization of the pituitary gland and the hypothalamo-pituitary connections. PITUITARY GLAND PITUITARY DEVELOPMENT The pituitary gland is a complex gland consisting of hormone producing adenoid (glandular) cells (anterior pituitary) and the axon terminals of neurosecretory cells originating in the hypothalamus (posterior pituitary). The anterior pituitary (or adenohypophysis) develops from an ectodermal pouch (Rathke s pouch) originating from the epithelial roof of the oral cavity, and the origin of the posterior pituitary (or neurohypophysis) is the neural ectoderm at the base of the third ventricle.while the anterior pituitary loses contact with the oral cavity during development, the posterior pituitary stays connected with the base of the hypothalamus. The two components of the gland are joined together and cradled in a recess in the sphenoid bone called the sella turcica (turkish saddle) at the base of the middle cranial fossa. The gland is enclosed (and separated from the) by the reflection of the dura mater. An extension of the base of brain the hypothalamus called the neural stalk penetrates the dura and, through the median eminence, connects the gland with the base of the hypothalamus. So how does such a complex amalgam of cells communicates and seamlessly
integrates its function with the hypothalamus? The key to the integration of the hypothalamopituitary axis is the organization of the pituitary blood supply. ANTERIOR PITUITARY HORMONES Seven important protein hormones plus several less important ones are secreted by the anterior pituitary. The hormones of the anterior pituitary play major roles in the control of physiological functions throughout the body Growth hormone (GH) promotes growth of the entire body by affecting protein formation, cell multiplication, and cell differentiation. Adrenocorticotropic hormone (ACTH) controls the secretion of some of the adrenocortical hormones, which affect the metabolism of glucose, proteins, and fats. Thyroid-stimulating hormone (TSH) controls the rate of secretion of thyroxine and tri-iodothyronine by the thyroid gland, and these hormones control the rates of most intracellular chemical reactions in the body. Prolactin(PRL) promotes mammary gland development and milk production. Two separate gonadotropic hormones, follicle-stimulating hormone (FSH) and luteinizing hormone(lh), control growth of the ovaries and testes, as well as their hormonal and reproductive activities. Melanocyte stimulating hormone(msh) is also produced by it to act on melanocyte producing melanin. Other brain peptides like enkephalins are also produced by anterior pituitary. Posterior Pituitary Gland and Its Relation to the Hypothalamus The posterior pituitary does not produce its own hormones; instead, it stores two hormones vasopressin and oxytocin that are produced by neurons in the hypothalamus. The posterior pituitary gland, also
called the neurohypophysis, is composed mainly of glial-like cells called pituicytes. The pituicytes do not secrete hormones; they act simply as a supporting structure for large numbers of terminal nerve fibers and terminal nerve endings from nerve tracts that originate in the supraoptic and paraventricular nuclei of the hypothalamus. These tracts pass to the neurohypophysis through the pituitary stalk (hypophysial stalk). The nerve endings lie on the surfaces of capillaries, where they secrete two posterior pituitary hormones: (1) antidiuretic hormone (ADH), also called vasopressin, and (2) oxytocin.( ADH is formed primarily in the supraoptic nuclei, whereas oxytocin is formed primarily in the paraventricular nuclei ).When nerve impulses are transmitted downward along the fibers from the supraoptic or paraventricular nuclei, the hormone is immediately released from the secretory granules in the nerve endings by the usual secretory mechanism of exocytosis and is absorbed into adjacent capillaries. Hormones of Posterior Pituitary ADH or Vasopressin, plays an important role in the body s water and electrolyte economy. Thus, ADH release promotes the reabsorption of water from the urine in the kidneys. Through this mechanism, the body reduces urine volume and conserves water. ADH release from the pituitary is controlled by the concentration of sodium in the blood as well as by blood volume and blood pressure. Oxytocin, the second hormone stored in the posterior pituitary, stimulates the contractions of the uterus during childbirth. Stimulation of the cervix in a pregnant woman elicits nervous signals that pass to the hypothalamus and cause increased secretion of oxytocin. It also plays an especially important role in lactation, oxytocin causes milk to be expressed from the alveoli into the ducts of the breast so that the
baby can obtain it by suckling. This mechanism works as follows: The suckling stimulus on the nipple of the breast causes signals to be transmitted through sensory nerves to the oxytocin neurons in the paraventricular and supraoptic nuclei in the hypothalamus,which causes release of oxytocin by the posterior pituitary gland. The oxytocin is then carried by the blood to the breasts, where it causes contraction of myoepithelial cells that lie outside of and form a latticework surrounding the alveoli of the mammary glands. In less than a minute after the beginning of suckling, milk begins to flow. This mechanism is called milk letdown or milk ejection Posterior Pituitary Hormone Release The main stimulus to ADH release is an increase in plasma osmolality which is detected by osmoreceptors (waterreceptors) in the hypothalamus. Once plasma osmolality is returned to normal, a negative feedback mechanism inhibits further ADH release. The other important stimulus to ADH release is a reduction in the effective circulating volume (e.g. in haemorrhage). This is detected by baroreceptors (pressure receptors) in the aortic arch and carotid sinus. Suckling is the main stimulus to the release of oxytocin from hypothalamus which in turn stimulates the secretion of milk from the milk ducts. Regulation of pituitary hormone secretion A. Neural control As mentioned above, secretion of pituitary hormones is controlled by neural stimuli that originate at the periphery or in the central nervous system. An excellent example of the peripheral control of pituitary hormone is the release of oxytocin and prolactin during nursing. The suckling of a baby stimulates sensory nerves and activates the afferent pathway to the hypothalamus. The hypothalamus responds
with the release of oxytocin in the posterior pituitary.oxytocin acts on the smooth muscle cells in the ducts of the mammary gland to expel the milk. As mentioned, the stimuli originating in the CNS can also stimulate pituitary hormone release. For example, many lactating mothers, when thinking about their baby, experience the ejection of a small amount of milk from the lactiferous ducts. This is brought about by the release of oxytocin in response to the mental images of the baby. Similarly, stimuli originating in the CNS during the REM phase of sleep induce the release of GHRH that results in the release of GH. Similarly,stimuli originating in the hypothalamic centers controlling circadian rhythms induce release of CRH approximately a couple of hours before waking to stimulate ACTH release. The opposite is true just before and/or at the beginning of sleep. B. Negative and positive feedback control Often, target tissues for the anterior pituitary hormones are glands themselves. The hormones secreted by these glands can inhibit/ stimulate the release of their tropic hormone or its tropic hormone releasing hormone. For example, FSH and LH stimulate production of sex hormones. Estradiol, progesterone and testosterone can inhibit/ stimulate both the release of gonadotropins as well as the release of GnRH. Regulation of adrenal medullary secretion by nerves Adrenal medullary secretion increase in response to the nerve stimuli that activate the sympathetic nervous system and is part of the diffuse sympathetic discharge that occurs in emergency flight or fight situations. Thus secretion increases in response to stress, pain, hypoglycemia, hypovolemia, hypotension, hypoxia, and strenuous exercise.these stimuli are sensed by the central nervous system and the responses are initiated in the hypothalamus and brainstem.
Release of acetylcholine by the greater splanchnic nerve depolarizes chromaffin cells, intracellular calcium concentration increases, and catecholamines are released by exocytosis. SUMMARY Neuro-endocrine and endocrine glands are able to synthesize, accumulate and release of varieties of hormones into circulation at optimal levels for their physiological actions in the target tissue. Their optimal levels are regulated by nervous system etc. The specialized neuro-endocrine cells of hypothalamus present in groups called nuclei produced neuro-hormones under the influence of higher brain centers. These neuro-hormones are called hypothalamic releasing and release inhibiting hormones as well as octapeptides. These hormones also control the endocrine activities of anterior pituitary through hypothalamo-pituitary axis and nerve tracts in case of posterior pituitary respectively.