TDEC 5TH SEM

MAJOR PAOER-5.3

HYPOTHALMO-
HYPOPHYSIAL AXIS
BY DR. LUNA
PHUKAN
The hypothalamus is a portion of the brain that contains a number of small
nuclei with a variety of functions. One of the most important functions of
the hypothalamus is to link the nervous system to the endocrine system via
the pituitary gland. The hypothalamus is located below the thalamus and is
part of the limbic system In the terminology of neuroanatomy, it forms the
ventral part of the diencephalon. All vertebrate brains contain a
hypothalamus. In humans, it is the size of an almond.

The hypothalamus is responsible for the regulation of certain metabolic

processes and other activities of the autonomic nervous system. It
synthesizes and secretes certain neurohormones, called releasing hormones
or hypothalamic hormones, and these in turn stimulate or inhibit the
secretion of hormones from the pituitary gland. The hypothalamus controls
body temperature, hunger, important aspects of parenting and attachment
behaviours, thirst, fatigue, sleep, and circadian rhythms.
Hypothalamo-hypophysal axis means the connecting portion between
hypothelamas and both anterior and posterior pituitary which consists
of nerve fibers, blood vessels , neurons .This portion or axis control
and release of various hormones which controls all metabolic and
physiological activity of body.

Hypothelamo- hypophysal axis is divided into 4 parts

1. The hypothalamic–pituitary–adrenal axis

2. The hypothalamic–pituitary–gonadal axis (HPG axis)

3. hypothalamic–pituitary–thyroid axis (HPT),

and the

4.hypothalamic–neurohypophyseal system are the four major neuro

endocrine system
Hypothalamo-Hypophyseal System
A collection of NEURONS, tracts of NERVE FIBERS,
endocrine tissue, and blood vessels in the
HYPOTHALAMUS and the PITUITARY GLAND. This
hypothalamo-hypophyseal portal circulation
provides the mechanism for hypothalamic
neuroendocrine (HYPOTHALAMIC HORMONES)
regulation of pituitary function and the release of
various PITUITARY HORMONES into the systemic
circulation to maintain HOMEOSTASIS
1.The hypothalamic–pituitary–adrenal axis
(HPA axis or HTPA axis) is a complex set of
direct influences and feedback interactions
among three components: the hypothalamus,
the pituitary gland (a pea-shaped structure
located below the thalamus), and the adrenal
(also called "suprarenal") glands (small, conical
organs on top of the kidney
These organs and their interactions constitute the HPA
axis, a major neuroendocrine system that controls
reactions to stress and regulates many body processes,
including digestion, the immune system, mood and
emotions, sexuality, and energy storage and expenditure.
It is the common mechanism for interactions among
glands, hormones, and parts of the midbrain that mediate
the general adaptation syndrome While steroid hormones
are produced mainly in vertebrates, the physiological role
of the HPA axis and corticosteroids in stress response is so
fundamental that analogous systems can be found in
invertebrates and monocellular organisms as well
Anatomy
The key elements of the HPA axis are:

The paraventricular nucleus of the hypothalamus, which contains

neuroendocrine neurons which synthesize and secrete vasopressin
and corticotropin-releasing hormone (CRH). These two peptides
regulate:
The anterior lobe of the pituitary gland. In particular, CRH and
vasopressin stimulate the secretion of adrenocorticotropic hormone
(ACTH), once known as corticotropin. ACTH in turn acts on:
the adrenal cortex, which produces glucocorticoid hormones
(mainly cortisol in humans) in response to stimulation by ACTH.
Glucocorticoids in turn act back on the hypothalamus and pituitary
(to suppress CRH and ACTH production) in a negative feedback
CRH and vasopressin are released from neurosecretory nerve terminals at the
median eminence. CRH is transported to the anterior pituitary through the
portal blood vessel system of the hypophyseal stalk and vasopressin is
transported by axonal transport to the posterior pituitary gland. There, CRH
and vasopressin act synergistically to stimulate the secretion of stored ACTH
from corticotrope cells. ACTH is transported by the blood to the adrenal cortex
of the adrenal gland, where it rapidly stimulates biosynthesis of corticosteroids
such as cortisol from cholesterol.
Cortisol is a major stress hormone and has effects on many tissues in the body,
including the brain. In the brain, cortisol acts on two types of receptor –
mineralocorticoid receptors and glucocorticoid receptors, and these are
expressed by many different types of neurons. One important target of
glucocorticoids is the hypothalamus, which is a major controlling centre of the
HPA axis.
Vasopressin can be thought of as "water conservation hormone" and is also
known as "antidiuretic hormone." It is released when the body is dehydrated
and has potent water-conserving effects on the kidney. It is also a potent
vasoconstrictor.
Important to the function of the HPA axis are some of the feedback loops:
Cortisol produced in the adrenal cortex will negatively feedback to inhibit both
the hypothalamus and the pituitary gland. This reduces the secretion of CRH
and vasopressin, and also directly reduces the cleavage of
proopiomelanocortin (POMC) into ACTH and β-endorphins.
Epinephrine and norepinephrine (E/NE) are produced by the
adrenal medulla through sympathetic stimulation and the local
effects of cortisol (upregulation enzymes to make E/NE). E/NE will
positively feedback to the pituitary and increase the breakdown of
POMCs into ACTH and β-endorphins.
Function
Release of corticotropin-releasing hormone (CRH) from the
hypothalamus is influenced by stress, physical activity, illness, by
blood levels of cortisol and by the sleep/wake cycle (circadian
rhythm). In healthy individuals, cortisol rises rapidly after wakening,
The HPA axis has a central role in regulating many homeostatic systems in the
body, including the metabolic system, cardiovascular system, immune system,
reproductive system and central nervous systemAnatomical connections
between brain areas such as the amygdala, hippocampus, prefrontal cortex and
hypothalamus facilitate activation of the HPA axis.Sensory information arriving
at the lateral aspect of the amygdala is processed and conveyed to the
amygdala's central nucleus, which then projects out to several parts of the brain
involved in responses to fear. At the hypothalamus, fear-signaling impulses
activate both the sympathetic nervous system and the modulating systems of
the HPA axis.
Almost all secretion by the pituitary is controlled by either hormonal or nervous
signals from the hypothalamus. Indeed, when the pituitary gland is removed
from its normal position beneath the hypothalamus and transplanted to some
other part of the body, its rates of secretion of the different hormones (except
for prolactin) fall to very low levels.Secretion from the posterior pituitary is
controlled by nerve signals that originate in the hypothalamus and terminate in
the posterior pituitary. In contrast, secretion by the anterior pituitary is
controlled by hormones called
hypothalamic releasing and hypothalamic inhibitory hormones (or
factors) secreted within the hypothalamus and then conducted, as
shown in Figure to the anterior pituitary through minute blood
vessels called hypothalamic-hypophysial portal vessels. In the anterior
pituitary, these releasing and inhibitory hormones act on the
glandular cells to control their secretion
The hypothalamus receives signals from many sources in the nervous system. Thus, when a person is exposed
to pain, a portion of the pain signal is transmitted into the hypothalamus.

Hypothalamic-Hypophysial Portal Blood Vessels of the Anterior Pituitary Gland

The anterior pituitary is a highly vascular gland with extensive capillary
sinuses among the glandular cells.
Almost all the blood that enters these sinuses passes first through another
capillary bed in the lower hypothalamus. The blood then flows through small
hypothalamichypophysial portal blood vessels into the anterior pituitary
sinuses. Figure shows the lowermost portion of the hypothalamus, called
the median eminence, which connects inferiorly with the pituitary stalk.
Small arteries penetrate into the median eminence and then additional small
vessels return to its surface, coalescing to form the hypothalamic-
hypophysial portal blood vessels. These pass downward along the pituitary
stalk to supply blood to the anterior pituitary sinuses.
Hypothalamic-hypophysial
portal system
Hypothalamic Releasing and Inhibitory Hormones Are Secreted into the
Median Eminence.

Special neurons in the hypothalamus synthesize and

secrete the hypothalamic releasing and inhibitory
hormones that control secretion of the anterior pituitary
hormones. These neurons originate in various parts of
the hypothalamus and send their nerve fibers to the
median eminence and tuber cinereum, an extension of
hypothalamic tissue into the pituitary stalk
2.The hypothalamic–pituitary–gonadal axis (HPG axis)
refers to the hypothalamus, pituitary gland, and gonadal glands as if these
individual endocrine glands were a single entity. Because these glands often
act in concert, physiologists and endocrinologists find it convenient and
descriptive to speak of them as a single system.
The axis controls development, reproduction, and aging in animals. Gonadotropin-
releasing hormone (GnRH) is secreted from the hypothalamus by GnRH-expressing
neurons. The anterior portion of the pituitary gland produces luteinizing hormone (LH)
and follicle-stimulating hormone (FSH), and the gonads produce estrogen and
testosterone.
In oviparous organisms (e.g. fish, reptiles, amphibians, birds), the HPG axis is
commonly referred to as the hypothalamus-pituitary-gonadal-liver axis
(HPGL-axis) in females. Many egg-yolk and chorionic proteins are synthesized
heterologously in the liver, which are necessary for ovocyte growth and
development. Examples of such necessary liver proteins are vitellogenin and
choriogenin.
The HPA, HPG, and HPT axes are three pathways in which the hypothalamus
and pituitary direct neuroendocrine function.
HPG regulation in males, with the inhibin/activin system
playing a similar role on GnRH-producing cells.
Location and regulation
HPG regulation in males, with the inhibin/activin system playing a similar role on GnRH-
producing cells.
The hypothalamus is located in the brain and secretes GnRH.GnRH travels down the anterior
portion of the pituitary via the hypophyseal portal system and binds to receptors on the
secretory cells of the adenohypophysis. In response to GnRH stimulation these cells produce
LH and FSH, which travel into the blood stream.
These two hormones play an important role in communicating to the gonads. In females FSH
and LH act primarily to activate the ovaries to produce estrogen and inhibin and to regulate
the menstrual cycle and ovarian cycle. Estrogen forms a negative feedback loop by inhibiting
the production of GnRH in the hypothalamus.
Function :Reproduction
One of the most important functions of the HPG axis is to regulate reproduction by controlling the uterine and
ovarian cycles. In females, the positive feedback loop between estrogen and luteinizing hormone help to prepare
the follicle in the ovary and the uterus for ovulation and implantation. When the egg is released, the empty
follicle sac begins to produce progesterone to inhibit the hypothalamus and the anterior pituitary thus stopping
the estrogen-LH positive feedback loop. If conception occurs, the placenta will take over the secretion of
progesterone; therefore the mother cannot ovulate again.

If conception does not occur, decreasing excretion of progesterone will allow the
hypothalamus to restart secretion of GnRH. These hormone levels also control the uterine
(menstrual) cycle causing the proliferation phase in preparation for ovulation, the secretory
phase after ovulation, and menstruation when conception does not occur. The activation of
the HPG axis in both males and females during puberty also causes individuals to acquire
secondary sex characteristics.
3.The hypothalamic–pituitary–thyroid axis
(HPT axis for short, a.k.a. thyroid homeostasis or thyrotropic feedback control) is part of the
neuroendocrine system responsible for the regulation of metabolism and also responds to
stress.
As its name suggests, it depends upon the hypothalamus, the pituitary gland, and the
thyroid gland.
The hypothalamus senses low circulating levels of thyroid hormone (Triiodothyronine (T3)
and Thyroxine (T4)) and responds by releasing thyrotropin-releasing hormone (TRH). The
TRH stimulates the anterior pituitary to produce thyroid-stimulating hormone (TSH).

The TSH, in turn, stimulates the thyroid to produce thyroid hormone until levels in the blood
return to normal. Thyroid hormone exerts negative feedback control over the hypothalamus
as well as anterior pituitary, thus controlling the release of both TRH from hypothalamus and
TSH from anterior pituitary gland.

The HPA, HPG, and HPT axes are three pathways in which the hypothalamus and pituitary
direct neuroendocrine function.
The pituitary gland secretes thyrotropin (TSH; Thyroid Stimulating
Hormone) that stimulates the thyroid to secrete thyroxine (T4)
and, to a lesser degree, triiodothyronine (T3).
The major portion of T3, however, is produced in peripheral
organs, e.g. liver, adipose tissue, glia and skeletal muscle by
deiodination from circulating T4. Deiodination is controlled by
numerous hormones and nerval signals including TSH, vasopressin
and catecholamines.
Both peripheral thyroid hormones (iodothyronines) inhibit
thyrotropin secretion from the pituitary (negative feedback).
Consequently, equilibrium concentrations for all hormones are
attained.
Thank you