Overview of Endocrine System

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Structure and Function of the Endocrine System

The endocrine system, closely integrated with the nervous system, helps maintain internal
homeostasis and respond to external environments. Together, these systems are often referred to
as the neuroendocrine system. The traditional endocrine system includes glands that produce and
secrete hormones directly into the bloodstream, acting as chemical messengers within the body.

Endocrine Glands and Hormones

Endocrine glands are collections of specialized cells without ducts that produce hormones, which
have specific effects at hormone-receptor sites. While some organs function similarly to endocrine
glands and certain hormones act locally without entering the bloodstream, this section focuses on
traditional endocrine glands and hormones.
Key Characteristics of Hormones:

Produced in very small amounts

Secreted directly into the bloodstream

Travel through blood to specific receptor sites throughout the body

Increase or decrease normal metabolic cellular processes when interacting with receptor sites

Immediately broken down after exerting their effect

Mechanisms of Hormonal Action

Hormones can act in two primary ways:

1. Membrane-Receptor Interaction:

Hormones react with specific receptor sites on a cell membrane, stimulating intracellular
cyclic adenosine monophosphate (cAMP) to cause an effect.

Example: Insulin interacts with its receptor site, activating enzymes that alter cell membrane
permeability to glucose.

These hormones act quickly, often within seconds.

2. Intracellular Interaction:

Hormones enter the cell and react with intracellular receptor sites, changing messenger
RNA and affecting cellular DNA, which alters the cell's function.

Example: Estrogen enters the cell, changes messenger RNA, affecting DNA and cellular
function.

These hormones take longer to produce effects, such as the changes seen at puberty.

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 Functions and Regulation
The endocrine system regulates various functions including:

Growth and development

Reproduction

Energy use

Electrolyte balance

This system, in conjunction with the nervous system, ensures homeostasis by tightly regulating
body processes within a narrow range of normal limits. Overproduction or underproduction of
hormones can significantly impact body activities and the functioning of other hormones within the
system.

Endocrine Glands with Associated Hormones and Clinical Effects

HORMONES
GLAND PRINCIPAL EFFECTS
PRODUCED

Increases glucose levels, suppresses inflammatory and

Adrenal cortex Cortisol
immune reactions

Aldosterone Sodium retention, potassium excretion

Secretin, Decreases gastric movement, stimulates bile and

Intestine
cholecystokinin pancreatic juice secretion

Kidney (juxtaglomerular
Erythropoietin Increases red blood cell production
cells)

Stimulates increase in blood pressure and vascular

Renin
volume

Promotes secondary sex characteristics, prepares the

Ovaries Estrogen, progesterone
female body for pregnancy

Insulin, glucagon, Regulation of glucose, fat metabolism (islets of

Pancreas
somatostatin Langerhans)

Parathyroid glands Parathyroid hormone Increases serum calcium levels

Affects secretion of hypothalamic hormones, particularly

Pineal gland Melatonin
gonadotropin-releasing hormone

Estrogens, Maintains fetal growth and development, prepares the

Placenta
progesterones body for delivery

Stomach Gastrin Stimulates stomach acid production

Testes Testosterone Stimulates secondary sex characteristics in males

Stimulates basal metabolic rate (how the body uses

Thyroid Thyroid hormone
energy)

Calcitonin Decreases serum calcium levels

The Hypothalamus
The hypothalamus is the central coordinating center for the nervous and endocrine responses to
internal and external stimuli. It 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. Often referred to as the “master gland” of the

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 neuroendocrine system, the hypothalamus was once considered secondary to the pituitary gland
due to the latter's numerous functions and protected location.

Functions and Sensitivity

The hypothalamus contains various neurocenters—areas specifically sensitive to certain stimuli—
that regulate several body functions, including:

Body temperature

Thirst

Hunger

Water retention

Blood pressure

Respiration

Reproduction

Emotional reactions

Situated at the base of the forebrain, the hypothalamus receives input from almost all areas of the
brain, including the limbic system and cerebral cortex. This strategic positioning allows the
hypothalamus to influence and be influenced by emotions and thoughts. Furthermore, it resides in a
region of the brain that is not well protected by the blood-brain barrier, enabling it to act as a sensor
to various electrolytes, chemicals, and hormones circulating in the body, which do not affect other
brain areas.

Maintenance of Homeostasis
The hypothalamus maintains internal homeostasis by:

Sensing blood chemistries

Stimulating or suppressing endocrine, autonomic, and CNS activity

Turning the autonomic nervous system and its effects on or off

Hormone Production and Secretion

The hypothalamus produces and secretes several releasing hormones or factors that stimulate the
pituitary gland. These include:

Growth hormone–releasing hormone (GHRH)

Thyrotropin-releasing hormone (TRH)

Gonadotropin-releasing hormone (GnRH)

Corticotropin-releasing hormone (CRH)

Prolactin-releasing hormone (PRH)

It also produces two inhibiting factors that regulate hormone production when levels become too
high:

Growth hormone release–inhibiting factor (somatostatin)

Prolactin-inhibiting factor (PIF)

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 Recent research suggests that PIF may actually be dopamine, a neurotransmitter. Patients taking
dopamine-blocking drugs often develop galactorrhea (inappropriate milk production) and breast
enlargement, theoretically because PIF is blocked, leading to continuous prolactin stimulation of
breast tissue and milk production. Research into the chemical structure of several releasing factors
is ongoing.

Connection to the Pituitary Gland

The hypothalamus connects to the pituitary gland through two networks:

1. Vascular Network: Carries hypothalamic releasing factors directly into the anterior pituitary.

2. Neurological Network: Delivers two hypothalamic hormones—antidiuretic hormone (ADH) and

oxytocin—to the posterior pituitary for storage. These hormones are released as needed by the
body when stimulated by the hypothalamus.

The Pituitary Gland

The pituitary gland, located in the skull in the bony sella turcica under a layer of dura mater, is
divided into three lobes: the anterior lobe, the posterior lobe, and the intermediate lobe. Historically
known as the body’s master gland due to its numerous critical functions, the pituitary gland
regulates many other endocrine glands through feedback mechanisms. However, it is now
understood that the hypothalamus has a greater direct regulatory effect over the neuroendocrine
system, including the stimulation of the pituitary gland to produce its hormones.

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 The Anterior Pituitary
The anterior pituitary produces six major hormones:

Growth hormone (GH)

Adrenocorticotropic hormone (ACTH)

Follicle-stimulating hormone (FSH)

Luteinizing hormone (LH)

Prolactin (PRL)

Thyroid-stimulating hormone (TSH) (also called thyrotropin)

These hormones are essential for regulating growth, reproduction, and certain metabolic
processes. Deficiency or overproduction of these hormones can disrupt these regulations. The
anterior pituitary hormones are released into the bloodstream in a rhythmic manner, often
influenced by time of day (diurnal rhythm) or physiological conditions such as exercise or sleep.

Their release is affected by:

CNS activity

Hypothalamic hormones

Hormones of the peripheral endocrine glands

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 Diseases that alter endocrine functioning

Various drugs that can disrupt homeostasis and cause an endocrine response

The diurnal rhythm involves the hypothalamus beginning the secretion of corticotropin-releasing
factor (CRF) in the evening, peaking around midnight, with the adrenocortical peak response
occurring between 6 and 9 AM, followed by a decline in levels throughout the day until evening.

The anterior pituitary also produces:

Melanocyte-stimulating hormone (MSH): Important for skin color changes in certain animals
and possibly nerve growth and development in humans.

Lipotropins: Stimulate fat mobilization but are not clearly isolated in humans.

The Posterior Pituitary

The posterior pituitary stores two hormones produced by the hypothalamus and deposited via
nerve axons:

Antidiuretic hormone (ADH): Also known as vasopressin, released in response to increased

plasma osmolarity or decreased blood volume. Osmoreceptors in the hypothalamus stimulate
its release.

Oxytocin: Stimulates uterine smooth muscle contraction in late pregnancy phases and causes
the milk release or “let down” reflex in lactating women. Its release is stimulated by various
hormones and neurological stimuli associated with labor and lactation.

The Intermediate Lobe

The intermediate lobe of the pituitary produces endorphins and enkephalins, released in response
to severe pain or stress. They occupy specific endorphin-receptor sites in the brainstem to block
the perception of pain and are also produced in peripheral tissues and other brain areas. These
hormones are released in response to:

Overactivity of pain nerves

Sympathetic stimulation

Transcutaneous stimulation

Guided imagery

Vigorous exercise

Endocrine Regulation
The production and release of hormones in the body must be tightly regulated to maintain
homeostasis. Hormones are released in small amounts to accomplish their specific functions, and
this fine-tuning is often regulated by the hypothalamus through a series of negative feedback
systems. Some hormones are controlled by different stimuli.

Hypothalamic–Pituitary Axis (HPA)

The hypothalamus, positioned in the brain, is stimulated by factors such as light, emotion, cerebral
cortex activity, and various chemical and hormonal stimuli. The hypothalamus and the pituitary
gland function closely together to maintain endocrine activity along the hypothalamic–pituitary axis
(HPA) through negative feedback systems.

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 Tight Regulation of Hormones:

Hormones are released in small, precise amounts to maintain homeostasis.

Regulation is often achieved through negative feedback systems.

Hypothalamic–Pituitary Axis (HPA):

The hypothalamus and pituitary gland closely work together to maintain endocrine activity.

Negative feedback mechanisms control hormone levels similarly to supply and demand in
business.

Example: When the hypothalamus detects a need for thyroid hormone, it secretes TRH,
which stimulates the anterior pituitary to release TSH, which in turn stimulates the thyroid
gland to produce thyroid hormone. Rising levels of thyroid hormone signal the hypothalamus
to stop TRH production, thus reducing TSH and thyroid hormone levels.

Complex Feedback System:

The feedback system is more intricate than initially thought.

The hypothalamus likely senses levels of releasing and stimulating hormones (e.g., TRH and
TSH), regulating their secretion.

The anterior pituitary may also regulate its own hormone production based on these levels.

This complex system provides backup controls if part of the HPA fails but can complicate
treatments like hormone replacement therapy.

Direct Regulation by the Hypothalamus:

Growth hormone and prolactin do not have target organs that produce hormones, so they
are regulated differently.

The hypothalamus responds to rising levels of these hormones by releasing inhibiting

factors (somatostatin for growth hormone and prolactin-inhibiting factor for prolactin).

The HPA uses negative feedback loops or direct inhibiting factors to regulate these
hormones.

Other Forms of Regulation

Hormones other than stimulating hormones are also released in response to various stimuli. For
example:

Pancreas: Produces and releases insulin, glucagon, and somatostatin from different cells in
response to varying blood glucose levels.

Parathyroid glands: Release parathyroid hormone in response to local calcium levels.

Juxtaglomerular cells in the kidney: Release erythropoietin and renin in response to decreased
blood pressure or decreased oxygenation of blood flowing into the glomerulus.

Gastrointestinal (GI) hormones: Released in response to local stimuli in areas of the GI tract,
such as acid, proteins, or calcium.

Thyroid gland: Produces and secretes calcitonin in direct response to serum calcium levels.

Prostaglandins: Released throughout the body in response to local stimuli in the tissues that
produce them.

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 Sympathetic nervous system activation: Directly causes the release of ACTH and
adrenocorticoid hormones to prepare the body for fight or flight.

Aldosterone: Released in response to ACTH but also directly in response to high potassium
levels.

Hypothalamic Hormones, Associated Anterior Pituitary Hormones, and Target

Organ Response
Hypothalamus Hormones Anterior Pituitary Hormones Target Organ Response

Stimulating Hormones

CRH (corticotropin-releasing
ACTH (adrenocorticotropic hormone) Adrenal corticosteroid hormones
hormone)

TRH (thyroid-releasing
TSH (thyroid-stimulating hormone) Thyroid hormone
hormone)

GHRH (growth hormone–

GH (growth hormone) Cell growth
releasing hormone)

GnRH (gonadotropin- LH and FSH (luteinizing hormone, Estrogen and progesterone (females),
releasing hormone) follicle-stimulating hormone) testosterone (males)

PRH (prolactin-releasing
Prolactin Milk production
hormone)

MSH (melanocyte-stimulating Melanin stimulation (color change in

-
hormone) animals, nerve growth in humans)

Inhibiting Hormones

Somatostatin (growth
- Stops release of GH
hormone–inhibiting factor)

PIF (prolactin-inhibiting
- Stops release of prolactin
factors)

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