Introduction to the Endocrine System 34
Learning Objectives
Upon completion of this chapter, you will be able to:
1. Label a diagram showing the glands of the traditional endocrine system and list the hormones produced by each.
2. Describe two theories of hormone action.
3. Discuss the role of the hypothalamus as the master gland of the endocrine system, including influences on the actions of the hypothalamus.
4. Outline a negative feedback system within the endocrine system and explain the ways that this system controls hormone levels in the body.
5. Describe the hypothalamic–pituitary axis (HPA) and what would happen if a hormone level was altered within the HPA.
Glossary of Key Terms
anterior pituitary: lobe of the pituitary gland that produces stimulating hormones, as well as growth hormone, prolactin, and melanocyte-stimulating hormone
diurnal rhythm: response of the hypothalamus and then the pituitary and adrenals to wakefulness, sleeping, and light exposure
glands: organized groups of specialized cells that secrete hormones, or chemical messengers, directly into the bloodstream to communicate within the body
hormones: chemical messengers working within the endocrine system to communicate within the body
hypothalamic–pituitary axis: interconnection of the hypothalamus and pituitary to regulate the levels of certain endocrine hormones through a complex series of negative feedback systems
hypothalamus: “master gland” of the neuroendocrine system; regulates both nervous and endocrine responses to internal and external stimuli
negative feedback system: control system in which increasing levels of a hormone lead to decreased levels of releasing and stimulating hormones, leading to decreased hormone levels, which stimulates the release of releasing and stimulating hormones; allows tight control of the endocrine system
neuroendocrine system: the combination of the nervous and endocrine systems, which work closely together to maintain regulatory control and homeostasis in the body
pituitary gland: gland found in the sella turcica of the brain; produces hormones, endorphins, and enkephalins and stores two hypothalamic hormones
posterior pituitary: lobe of the pituitary that receives antidiuretic hormone and oxytocin via nerve axons from the hypothalamus and stores them to be released when stimulated by the hypothalamus
releasing hormones or factors: chemicals released by the hypothalamus into the anterior pituitary to stimulate the release of anterior pituitary hormones
The endocrine system, in conjunction with the nervous system, works to maintain internal homeostasis and to integrate the body’s response to the external environment. Their activities and functions are so closely related that it is probably more correct to refer to them as the neuroendocrine system. However, this section deals with drugs affecting the
“traditional” endocrine system, which includes glands—organized groups of specialized cells that produce and secrete hormones, or chemical messengers, directly into the bloodstream to communicate within the body.
Some organs function like endocrine glands, but they are not considered part of the traditional endocrine system. In addition, certain hormones that influence body functioning are not secreted by endocrine glands. For example, prostaglandins are tissue hormones produced in various tissues; they do not enter the bloodstream, but exert their effects right in the area where they are released. Moreover, neurotransmitters, such as norepinephrine and dopamine, can be classified as hormones because they are secreted directly into the bloodstream for dispersion throughout the body. There also are many gastrointestinal (GI) hormones that are produced in GI cells and act locally. All of these hormones are addressed in the chapters most related to their effects.
1GI hormones are discussed in Part 11: Drugs Acting on the Gastrointestinal System. Neurotransmitters acting like hormones are discussed in Chapter 29: Introduction to the Autonomic Nervous System. The reproductive hormones are discussed in Chapter 39: Introduction to the Reproductive System. Hormones active in the inflammatory and immune response are discussed in Part 3: Drugs Acting on the Immune System. Specific traditional endocrine glands and hormones are discussed in Chapter 35 (hypothalamic and pituitary hormones), Chapter 36 (adrenocortical hormones), Chapter 37 (thyroid and parathyroid hormones), and Chapter 38 (pancreatic hormones).
Structure and Function of the Endocrine System
The endocrine system provides communication within the body and helps to regulate growth and development, reproduction, energy use, and electrolyte balance. The endocrine system is closely interconnected with the nervous system, and the two systems work to maintain homeostasis within the body to ensure maximum function and adequate response to various internal and external stressors.
Glands
The endocrine glands are collections of specialized cells that produce hormones that cause an effect at hormone receptor sites. These glands do not have ducts, so they secrete their hormones directly into the bloodstream. There are many endocrine glands in the body.
Table 34.1 lists the endocrine glands, the hormones that they produce, and the clinical effects that the hormones cause.
Table 34.1 Endocrine Glands with Associated Hormones and Clinical Effects
Hormones
Hormones are chemicals that are produced in the body and that meet specific criteria. All hormones:
Are produced in very small amounts Are secreted directly into the bloodstream
Travel through the blood to specific receptor sites throughout the body
Act to increase or decrease the normal metabolic cellular processes when they react with their specific receptor sites
Are immediately broken down
Hormones may act in two different ways. Some hormones react with specific receptor sites on a cell membrane to stimulate the nucleotide cyclic adenosine monophosphate (cyclic AMP) within the cell to cause an effect. For example, when insulin reacts with an insulin receptor site, it activates intracellular enzymes that cause many effects, including changing the cell membrane’s permeability to glucose. Hormones such as insulin that do not enter the cell but react with specific receptor sites on the cell membrane act very quickly—often within seconds—to produce an effect.
Other hormones, such as estrogen, actually enter the cell and react with a receptor site inside the cell to change messenger RNA, which enters the cell nucleus to affect cellular DNA and thereby alters the cell’s function. These hormones that enter the cell before they can cause an effect take quite a while to produce an effect. The full effects of estrogen may not be seen for months to years, as evidenced by the changes that occur at puberty. Because the neuroendocrine system tightly regulates the body’s processes within a narrow range of normal limits, overproduction or underproduction of any hormone can affect the body’s activities and other hormones within the system.
KEY POINTS
The endocrine system and the nervous system regulate body functions and maintain homeostasis largely with the help of hormones, which are chemicals produced within the body. Hormones increase or decrease cellular activity.
The endocrine system regulates growth and development, reproduction, energy use in the body, and electrolyte balance.
Hormones can react with receptors on the cell membrane to cause an immediate effect on a cell by altering enzyme systems near the cell membrane or they may enter the cell and react with receptor sites on messenger RNA, which then enters the nucleus and alters cell function.
The Hypothalamus
The hypothalamus is the coordinating center for the nervous and endocrine responses to internal and external stimuli. The hypothalamus constantly monitors the body’s homeostasis by analyzing input from the periphery and the central nervous system (CNS) and coordinating responses through the autonomic, endocrine, and nervous systems. In effect, it is the “master gland” of the neuroendocrine system. This title was once given to the pituitary gland because of its many functions and well-protected location (see The Pituitary Gland).
The hypothalamus has various neurocenters—areas specifically sensitive to certain stimuli—that regulate a number of body functions, including body temperature, thirst, hunger, water retention, blood pressure, respiration, reproduction, and emotional reactions.
Situated at the base of the forebrain the hypothalamus receives input from virtually all other areas of the brain, including the limbic system, cerebral cortex, and the special senses that are controlled by the cranial nerves—smell, sight, touch, taste, and hearing. Because of its positioning the hypothalamus is able to influence, and be influenced by, emotions and thoughts. The hypothalamus also is located in an area of the brain that is poorly protected by the blood–brain barrier, so it is able to act as a sensor to various electrolytes, chemicals, and hormones that are in circulation and do not affect other areas of the brain.
The hypothalamus maintains internal homeostasis by sensing blood chemistries and by stimulating or suppressing endocrine, autonomic, and CNS activity. In essence, it can turn the autonomic nervous system and its effects on or off. The hypothalamus also produces and secretes a number of releasing hormones or factors that stimulate the pituitary gland, which in turn stimulates or inhibits various endocrine glands throughout the body (Figure 34.1). These releasing hormones include growth hormone–releasing hormone, thyrotropin- releasing hormone (TRH), gonadotropin-releasing hormone, corticotropin-releasing hormone, and prolactin-releasing hormone. The hypothalamus also produces two inhibiting factors that act as regulators to shut off the production of hormones when levels become too high: Growth hormone (GH) release–inhibiting factor (somatostatin) and prolactin (PRL)-inhibiting factor (PIF). Recent research has indicated that PIF may actually be dopamine, a neurotransmitter. Patients who are taking dopamine-blocking drugs often develop galactorrhea (inappropriate milk production) and breast enlargement, theoretically because PIF also is blocked and prolactin (PRL) levels continue to rise, stimulating breast tissue and milk production. Research is ongoing about the chemical structure of several of the releasing factors.
FIGURE 34.1 The traditional endocrine system. The hypothalamus secretes releasing factors to stimulate the pituitary gland to produce stimulating factors that enter the circulation and react with specific target glands, which produce endocrine hormones.
The hypothalamus is connected to the pituitary gland by two networks: A vascular capillary network carries the hypothalamic-releasing factors directly into the anterior pituitary, and a neurological network delivers two other hypothalamic hormones—
antidiuretic hormone (ADH) and oxytocin—to the posterior pituitary to be stored. These hormones are released as needed by the body when stimulated by the hypothalamus.
KEY POINTS
As the “master gland” of the neuroendocrine system the hypothalamus helps to regulate the central and autonomic nervous systems and the endocrine system to maintain homeostasis.
The hypothalamus produces stimulating and inhibiting factors that travel to the anterior pituitary through a capillary system to stimulate the release of pituitary hormones or block the production of certain pituitary hormones when levels of target hormones get too high.
The hypothalamus is connected to the posterior pituitary by a nerve network that delivers the hypothalamic hormones ADH and oxytocin to be stored in the posterior pituitary until the hypothalamus stimulates their release.
The Pituitary Gland
The pituitary gland is located in the skull in the bony sella turcica under a layer of dura mater. It is divided into three lobes: An anterior lobe, a posterior lobe, and an intermediate lobe. Traditionally, the anterior pituitary was known as the body’s master gland because it has so many important functions and, through feedback mechanisms, regulates the function of many other endocrine glands. In addition, its unique and protected position in the brain led early scientists to believe that it must be the chief control gland. However, as knowledge of the endocrine system has grown, scientists now designate the hypothalamus as the master gland because it has even greater direct regulatory effects over the neuroendocrine system, including stimulation of the pituitary gland to produce its hormones.
The Anterior Pituitary
The anterior pituitary produces six major hormones: GH, adrenocorticotropic hormone (ACTH), follicle-stimulating hormone, luteinizing hormone, PRL, and thyroid-stimulating hormone (TSH, also called thyrotropin) (Table 34.2; see also Figure 34.1). These hormones are essential for the regulation of growth, reproduction, and some metabolic processes. Deficiency or overproduction of these hormones disrupts this regulation.
Table 34.2 Hypothalamic Hormones, Associated Anterior Pituitary Hormones, and Target Organ Response
CRH, corticotropin-releasing hormone; ACTH, adrenocorticotropic hormone; TRH, thyroid-releasing hormone;
TSH, thyroid-stimulating hormone; GHRH, growth hormone–releasing hormone; GH, growth hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; PRH, prolactin- releasing hormone; PRL, prolactin; MSH, melanocyte-stimulating hormone.
The anterior pituitary hormones are released in a rhythmic manner into the bloodstream. Their secretion varies with time of day (often referred to as diurnal rhythm) or with physiological conditions such as exercise or sleep. Their release is affected by activity in the CNS, by hypothalamic hormones, by hormones of the peripheral endocrine glands, by certain diseases that can alter endocrine functioning, and by a variety of drugs, which can directly or indirectly upset the homeostasis in the body and cause an endocrine response. Normally, diurnal rhythm occurs when the hypothalamus begins secretion of corticotropin-releasing factor (CRF) in the evening, peaking at about midnight;
adrenocortical peak response is between 6 and 9 AM; levels fall during the day until evening, when the low level is picked up by the hypothalamus and CRF secretion begins again.
The anterior pituitary also produces melanocyte-stimulating hormone (MSH) and various lipotropins. MSH plays an important role in animals that use skin color changes as an adaptive mechanism. It also might be important for nerve growth and development in humans. Lipotropins stimulate fat mobilization but have not been clearly isolated in humans.
The Posterior Pituitary
The posterior pituitary stores two hormones that are produced by the hypothalamus and deposited in the posterior lobe via the nerve axons where they are produced. These two hormones are ADH, also referred to as vasopressin, and oxytocin. ADH is directly released in response to increased plasma osmolarity or decreased blood volume (which often results in increased osmolarity). The osmoreceptors in the hypothalamus stimulate the release of ADH. Oxytocin stimulates uterine smooth muscle contraction in late phases of pregnancy and also causes milk release or “let-down” reflex in lactating women. Its release is stimulated by various hormones and neurological stimuli associated with labor and with lactation.
The Intermediate Lobe
The intermediate lobe of the pituitary produces endorphins and enkephalins, which are released in response to severe pain or stress and occupy specific endorphin receptor sites in the brainstem to block the perception of pain. These hormones are also produced in peripheral tissues and in other areas of the brain. They are released in response to overactivity of pain nerves, sympathetic stimulation, transcutaneous stimulation, guided imagery, and vigorous exercise.
KEY POINTS
The pituitary gland has three lobes:
The anterior lobe produces stimulating hormones in response to hypothalamic stimulation.
The posterior lobe of the pituitary stores ADH and oxytocin, which are two hormones produced by the hypothalamus.
The intermediate lobe of the pituitary produces endorphins and enkephalins to modulate pain perception.
Endocrine Regulation
The production and release of hormones needs to be tightly regulated within the body.
Hormones are released in small amounts to accomplish what needs to be done to maintain homeostasis within the body. The fine-tuning and regulation of hormone release through the hypothalamus are often regulated by a series of negative feedback systems. Other hormones are not controlled in this fashion but respond to other direct stimuli.
Hypothalamic–Pituitary Axis
Because of its position in the brain the hypothalamus is stimulated by many things, such as light, emotion, cerebral cortex activity, and a variety of chemical and hormonal stimuli.
Together, the hypothalamus and the pituitary function closely to maintain endocrine activity along what is called the hypothalamic–pituitary axis (HPA) using a series of negative feedback systems.
A negative feedback system works much like the law of supply and demand in business. In business, when there is an adequate supply of a product, production of that product will slow down because there is an adequate supply and no current demand for it.
When the supply is used up, demand will increase, and so production will pick up.
Production continues until the supply is adequate and demand is reduced. When the hypothalamus senses a need for a particular hormone—for example, thyroid hormone—it secretes the releasing factor TRH directly into the anterior pituitary. In response to the TRH the anterior pituitary secretes TSH, which in turn stimulates the thyroid gland to produce thyroid hormone. When the hypothalamus senses the rising levels of thyroid hormone, it stops secreting TRH, resulting in decreased TSH production and subsequent reduced thyroid hormone levels. The hypothalamus, sensing the falling thyroid hormone levels, secretes TRH again. The negative feedback system continues in this fashion, maintaining the levels of thyroid hormone within a relatively narrow range of normal (Figure 34.2).
FIGURE 34.2 Negative feedback system. Thyroid hormone levels are regulated by a series of negative feedback systems influencing thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), and thyroid hormone levels.
It is thought that this feedback system is more complex than once believed. The hypothalamus probably also senses TRH and TSH levels and regulates TRH secretion
within a narrow range, even if thyroid hormone is not produced. The anterior pituitary may also be sensitive to TSH levels and thyroid hormone, regulating its own production of TSH. This complex system provides backup controls and regulation if any part of the HPA fails. This system also can create complications, especially when there is a need to override or interact with the total system, as is the case with hormone replacement therapy or the treatment of endocrine disorders. Supplying an exogenous hormone, for example, may increase the hormone levels in the body, but then may affect the HPA to stop production of releasing and stimulating hormones, leading to a decrease in the body’s normal production of the hormone.
Two of the anterior pituitary hormones (i.e., GH and PRL) do not have a target organ to produce hormones and so cannot be regulated by the same type of feedback mechanism.
The hypothalamus in this case responds directly to rising levels of GH and PRL. When levels rise the hypothalamus releases the inhibiting factors somatostatin and PIF directly to inhibit the pituitary’s release of GH and PRL, respectively. The HPA functions through negative feedback loops or the direct use of inhibiting factors to constantly keep these hormones regulated.
Other Forms of Regulation
Hormones other than stimulating hormones also are released in response to stimuli. For example, the pancreas produces and releases insulin, glucagon, and somatostatin from different cells in response to varying blood glucose levels and to stimulatory factors released by the GI tract. The parathyroid glands release parathyroid hormone, or parathormone, in response to local calcium levels. The juxtaglomerular cells in the kidney release erythropoietin and renin in response to decreased pressure or decreased oxygenation of the blood flowing into the glomerulus. GI hormones are released in response to local stimuli in areas of the GI tract, such as acid, proteins, or calcium. The thyroid gland produces and secretes another hormone, called calcitonin, in direct response to serum calcium levels.
Many different prostaglandins are released throughout the body in response to local stimuli in the tissues that produce them. Activation of the sympathetic nervous system directly causes release of ACTH and the adrenocorticoid hormones to prepare the body for fight or flight. Aldosterone, an adrenocorticoid hormone, is released in response to ACTH but also is released directly in response to high potassium levels.
As more is learned about the interactions of the nervous and endocrine systems, new ideas are being formed about how the body controls its intricate homeostasis. When administering any drug that affects the endocrine or nervous systems, it is important for the nurse to remember how closely related all of these activities are. Expected or unexpected adverse effects involving areas of the endocrine and nervous systems often occur.