NEUROENDOCRINE SYSTEM-

The central neuroendocrine systems serve as an interface between the brain and

many of the peripheral endocrine systems. Hypothalamic control of anterior

pituitary systems regulating stress, basal metabolism, growth, reproduction, and

lactation. Each of these systems involves one or more hypothalamic-releasing or

inhibiting hormones, released from hypothalamic neurons that terminate in the

portal capillary vasculature that projects from the median eminence at the base

of the hypothalamus to the anterior pituitary gland.

HYPOTHALAMUS IS THE CENTRAL NEUROENDOCRINE ORGAN

The hypothalamus, located at the most rostral region of the brainstem in the

diencephalon, is a key center regulating numerous and diverse physiological

functions, including growth, metabolism, stress responses, reproduction,

osmoregulation, and circadian rhythms. All these functions are critically

involved in maintaining the homeostasis of the organism and in coordinating the

occurrence and timing of physiological functions with the appropriate

environmental conditions.

In order to accomplish this, the hypothalamus acts as an integrator, receiving

converging inputs from the sensory and autonomic systems related to the

internal and external environment of the organism. The hypothalamus responds

rapidly to this convergent information by changing its output of

neurotransmitters and neuropeptides, which in turn effect change at its targets

within the central nervous system (CNS), the pituitary gland, and the

bloodstream.

ENDOCRINE SYSTEM-

There are two types of glands exocrine glands and endocrine glands. Exocrine

glands release chemicals into ducts, which carry them to their targets, mostly on

the surface of the body, for example; sweat glands. Endocrine glands are

generally ductless gland that releases their chemical into the circulatory system

Hormones are molecules that are produced by endocrine glands, including the

hypothalamus, pituitary gland, adrenal glands, gonads, (i.e., testes and ovaries),

thyroid gland, parathyroid glands, and pancreas. The term “endocrine” implies

that in response to specific stimuli, the products of those glands are released into

the bloodstream. The hormones then are carried via the blood to their target

cells. Some hormones have only a few specific target cells, whereas other

hormones affect numerous cell types throughout the body. The target cells for

each hormone are characterized by the presence of certain docking molecules

(i.e., receptors) for the hormone that are located either on the cell surface or

inside the cell. The interaction between the hormone and its receptor triggers a

cascade of biochemical reactions in the target cell that eventually modify the

cell’s function or activity.

The feedback mechanism of the endocrine gland-

 HYPOTHALAMUS

Releasing hormone

ANTERIOR PITUITARY

Pituitary hormone

TARGET GLAND

Pituitary gland

The pituitary gland is located in a bony cavity called sella tunica and is attached

to the hypothalamus by a stalk. It is divided anatomically into an

adenohypophysis and a neurohypophysis. Adenohypophysis consists of two

portions, pars distalis and pars Intermedia. The parts distal region of the

pituitary, commonly called the anterior pituitary, produces growth hormone

(GH), prolactin (PRL), thyroid stimulating hormone (TSH),

adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH), and follicle-

stimulating hormone (FSH).

Pars intermedia secretes only one hormone called melanocyte-stimulating

hormone (MSH). However, in humans, the pars intermedia is almost merged

with pars distalis. Neurohypophysis (pars nervosa) also known as posterior

pituitary, stores and releases two hormones called oxytocin and vasopressin,
which are actually synthesized by the hypothalamus and transported axonally to

the neurohypophysis.

• Over-secretion of GH stimulates abnormal growth of the body leading

to gigantism and low secretion of GH results in stunted growth

resulting in pituitary dwarfism.

• Prolactin regulates the growth of the mammary glands and the

formation of milk in them.

• TSH stimulates the synthesis and secretion of thyroid hormones from

the thyroid gland.

• ACTH stimulates the synthesis and secretion of steroid hormones

called glucocorticoids from the adrenal cortex. LH and FSH stimulate

gonadal activity and hence are called gonadotropins.

• In males, LH stimulates the synthesis and secretion of hormones

called androgens from the testis. In males, FSH and androgens

regulate spermatogenesis.

• In females, LH induces ovulation of fully mature follicles (Graafian

follicles) and maintains the corpus luteum, formed from the remnants

of the Graafian follicles after ovulation.

 • FSH stimulates the growth and development of ovarian follicles in

females.MSH acts on the melanocytes (melanin-containing cells) and

regulates the pigmentation of the skin.

• Oxytocin acts on the smooth muscles of our body and stimulates their

contraction. In females, it stimulates a vigorous contraction of the

uterus at the time of childbirth, and milk ejection from the mammary

gland.

• Vasopressin acts mainly in the kidney and stimulates.

Thyroid

The thyroid gland is composed of two lobes which are located on either side of

the trachea. Both lobes are interconnected with a thin flap of connective tissue

called the isthmus. The thyroid gland is composed of follicles and stromal tissues.

Each thyroid follicle is composed of follicular cells, enclosing a cavity. These

follicular cells synthesize two hormones, tetraiodothyronine or thyroxine (T4)

and triiodothyronine (T3).

Iodine is essential for the normal rate of hormone synthesis in the thyroid.

Deficiency of iodine in our diet results in hypothyroidism and enlargement of the

thyroid gland, commonly called goiter. Hypothyroidism during pregnancy causes

defective development and maturation of the growing baby leading to stunted

growth (cretinism), mental retardation, low intelligence quotient, abnormal

skin, deaf-mutism, etc. In adult women, hypothyroidism may cause a menstrual

cycle to become irregular.

Due to a tumor of the thyroid gland or due to the development of nodules of the

thyroid glands, the rate of synthesis and secretion of the thyroid hormones is

increased to abnormally high levels leading to a condition called

hyperthyroidism which adversely affects the body’s physiology.

Thyroid hormones play an important role in the regulation of the basal metabolic

rate.

These hormones also support the process of red blood cell formation. Thyroid

hormones control the metabolism of carbohydrates, proteins, and fats.

The maintenance of water and electrolyte balance is also influenced by thyroid

hormones. The thyroid gland also secretes a protein a hormone called

thyrocalcitonin (TCT) which regulates blood calcium levels.

Thyroid hormones play an important role in the regulation of the basal metabolic

rate. These hormones also support the process of red blood cell formation.

Thyroid hormones control the metabolism of carbohydrates, proteins, and fats.

The maintenance of water and electrolyte balance is also influenced by thyroid

hormones. The thyroid gland also secretes a protein hormone called

thyrocalcitonin (TCT) which regulates blood calcium levels.

Adrenal Gland
Our body has one pair of adrenal glands, one at the anterior part of each

kidney. The gland is composed of two types of tissues. The centrally located

tissue is called the adrenal medulla, and outside this lies the adrenal cortex. The

adrenal medulla secretes two hormones called adrenaline or epinephrine and

noradrenaline or norepinephrine. These are commonly called catecholamines.

Adrenaline and noradrenaline are rapidly secreted in response to the stress of any

kind and during emergency situations and are called emergency hormones or

hormones of Fight or Flight. These hormones increase alertness, pupillary

dilation, piloerection (raising of hair), sweating, etc. Both hormones increase the

heartbeat, the strength of heart contraction, and the rate of respiration.

Catecholamines also stimulates the breakdown of glycogen resulting in an

increased concentration of glucose in the blood. In addition, they also stimulate

the breakdown of lipids and proteins.

The adrenal cortex can be divided into three layers, called zona reticularis (inner

layer), zona fasciculata (middle layer), and zona glomerulosa (outer layer). The

adrenal cortex secretes many hormones, commonly called corticoids. The

corticoids, which are involved in carbohydrate metabolism are called

glucocorticoids. In our body, cortisol is the main glucocorticoid. Corticoids,

which regulate the balance of water and electrolytes in our body are called

mineralocorticoids. Aldosterone is the main mineralocorticoid in our body.

Glucocorticoids stimulate gluconeogenesis, lipolysis, and proteolysis; and inhibit

cellular uptake and utilization of amino acids. Cortisol is also involved in

maintaining the cardiovascular system as well as the kidney functions.

Glucocorticoids, particularly cortisol, produce anti-inflammatory reactions and

suppress the immune response. Cortisol stimulates RBC production. Aldosterone

acts mainly at the renal tubules and stimulates the reabsorption of Na+ and water

and the excretion of K+ and phosphate ions. Thus, aldosterone helps in the

maintenance of electrolytes, body fluid volume, osmotic pressure, and blood

pressure. Small amounts of androgenic steroids are also secreted by the adrenal

cortex which plays a role in the growth of axial hair, pubic hair, and facial hair

during puberty.

Pancreas

Pancreas is a composite gland that acts as both an exocrine and endocrine gland.
The endocrine pancreas consists of ‘Islets of Langerhans’.

The two main types of cells in the Islet of Langerhans are called α-cells and β-
cells. The α-cells secrete a hormone called glucagon, while the β-cells secrete
insulin.

Glucagon is a peptide hormone and plays an important role in maintaining

normal blood glucose levels. Glucagon acts mainly on the liver cells
(hepatocytes) and stimulates glycogenolysis resulting in increased blood sugar
(hyperglycemia). In addition, this hormone stimulates the process of
gluconeogenesis which also contributes to hyperglycemia. Glucagon reduces
cellular glucose uptake and utilization.

Thus, glucagon is a hyperglycaemic hormone. Insulin is a peptide hormone,

which plays a major role in the regulation of glucose homeostasis. Insulin acts
mainly on hepatocytes and adipocytes (cells of adipose tissue) and enhances
cellular glucose uptake and utilization.

As a result, there is a rapid movement of glucose from the blood to hepatocytes

and adipocytes resulting in decreased blood glucose levels (hypoglycemia).
Insulin also stimulates the conversion of glucose to glycogen (glycogenesis) in
the target cells. The glucose homeostasis in the blood is thus maintained jointly
by the two – insulin and glucagon.

Prolonged hyperglycemia leads to a complex disorder called diabetes mellitus

which is associated with the loss of glucose through urine and

The formation of harmful compounds known as ketone bodies. Diabetic patients

are successfully treated with insulin therapy.

Gonads-

A pair of testes are present in the scrotal sac (outside abdomen) of male

individuals. Testis performs dual functions as a primary sex organ as well as an

endocrine gland. Testis is composed of seminiferous tubules and stromal or

interstitial tissue. The Leydig cells or interstitial cells, which are present in the

intertubular spaces produce a group of hormones called androgens mainly

testosterone. Androgens regulate the development, maturation, and functions of

the male accessory sex organs like epididymis, vas deferens, seminal vesicles,

prostate gland, urethra, etc. These hormones stimulate muscular growth, growth

of facial and axillary hair, aggressiveness, low pitch of voice, etc. Androgens play

a major stimulatory role in the process of spermatogenesis (formation of

spermatozoa). Androgens act on the central neural system and influence male

sexual behavior (libido). These hormones produce anabolic (synthetic) effects on

protein and carbohydrate metabolism.

Females have a pair of ovaries located in the abdomen Ovary is the primary

female sex organ that produces one ovum during each menstrual cycle. In

addition, the ovary also produces two groups of steroid hormones called estrogen

and progesterone. Ovary is composed of ovarian follicles and stromal tissues. The

estrogen is synthesized and secreted mainly by the growing ovarian follicles.

After ovulation, the ruptured follicle is converted to a structure called corpus

luteum, which secretes mainly progesterone. Estrogens produce wide-ranging

actions such as stimulation of growth and activities of female secondary sex

organs, development of growing ovarian follicles, the appearance of female

secondary sex characters (e.g., the high pitch of voice, etc.), and mammary gland

development. Estrogens also regulate female sexual behavior. Progesterone

supports a pregnancy. Progesterone also acts on the mammary glands and

stimulates the formation of alveoli (sac-like structures which store milk) and milk

secretion.
The thymus gland is a lobular structure located between the lungs and

behind the sternum on the ventral side of the aorta. The thymus plays a major role

in the development of the immune system. This gland secretes the peptide

hormones called thymosins. Thymosins play a major role in the differentiation of

T-lymphocytes, which provide cell-mediated immunity. In addition, thymosins

also promote the production of antibodies to provide humoral immunity. Thymus

is degenerated in old individuals resulting in a decreased production of

thymosins. As a result, the immune responses of old persons become weak.

In humans, four parathyroid glands are present on the back side of the

thyroid gland, one pair each in the two lobes of the thyroid gland. The parathyroid

glands secrete a peptide hormone called parathyroid hormone (PTH). The

secretion of PTH is regulated by the circulating levels of calcium ions.

Parathyroid hormone (PTH) increases the Ca2+ levels in the blood. PTH acts on

bones and stimulates the process of bone resorption

(dissolution/demineralization). PTH also stimulates the reabsorption of Ca2+ by

the renal tubules and increases Ca2+ absorption from the digested food. It is, thus,

clear that PTH is a hypercalcemic hormone, i.e., it increases blood Ca2+ levels.

Along with TCT, it plays a significant role in calcium balance in the body.
 The pineal gland is located on the dorsal side of the forebrain. The Pineal

secretes a hormone called melatonin. Melatonin plays a very important role in the

regulation of a 24-hour (diurnal) rhythm of our body. For example, it helps in

maintaining the normal rhythms of the sleep-wake cycle, and body temperature.

In addition, melatonin also influences metabolism, pigmentation, the menstrual

cycle as well as our defense capability.

The complex pathway of the endocrine system

HYPOTHALAMUS

PITUITARY

GONADS
ADRENAL
THYROID

HPA AXIS HPT AXIS HPG AXIS

 various endocrine glands and their hormones, some hormones are controlled

directly by the metabolic pathways that they influence. For example, blood sugar

levels directly control insulin and glucagon release by the pancreas, and calcium

levels in the blood regulate PTH release.

Conversely, many hormones produced by target, glands are regulated by the

pituitary hormones, which in turn are controlled by hypothalamic hormones.

Examples of such regulatory hormonal cascades include the hypothalamic-

pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis,

and the hypothalamic-pituitary-thyroidal (HPT) axis.