Anterior Pituitary

Gland

Dr. Ali Alkaleel

MD. PhD
Pituitary: The Master Gland
The pituitary, a pea-sized gland, produces a number of hormones, each of which affects a specific part of the
body (a target organ or tissue). Because the pituitary controls the function of most other endocrine
glands, it is often called the master gland.

Hormone Target Organ or Tissue

Adrenocorticotropic hormone (ACTH) Adrenal glands
Antidiuretic hormone Kidney
Follicle-stimulating hormone Ovaries or testis
Growth hormone Muscles and bones
Luteinizing hormone Ovaries or testis
Oxytocin Uterus and mammary glands
Prolactin Mammary glands
Thyroid-stimulating hormone Thyroid gland
Anterior pituitary (Adenohypophysis):Weighing less than one gram!!
•A major organ of the endocrine system, the anterior pituitary, also called the
adenohypophysis, is the glandular, anterior lobe of the pituitary gland.
•The anterior pituitary regulates several physiological processes including stress, growth,
and reproduction….
•Its regulatory functions are achieved through the secretion of various peptide hormones
that act on target organs including the adrenal gland, liver, bone, thyroid gland, and gonads.
•The anterior pituitary itself is regulated by the hypothalamus and by negative feedback
from these target organs.
•Disorders of the anterior pituitary are generally classified by the presence of over- or under
production of pituitary hormones.
•For example, a prolactinoma is a pituitary adenoma that overproduces prolactin.
•In Sheehan's syndrome of postpartum hypopituitarism, the anterior pituitary uniformly
malfunctions and under produces all hormones.
•Proper function of the anterior pituitary and of the organs it regulates can often be
ascertained via blood tests that measure hormone levels.
Embryology:
The anterior pituitary arises from an invagination of the oral ectoderm and forms
Rathke's pouch. This contrasts with the posterior pituitary, which originates from
neuroectoderm.

Hormone secretion:

•The secretion of hormones from the anterior pituitary is controlled by inhibiting and releasing
factors secreted by neurons in the hypothalamus.
•These inhibiting and releasing factors are release into a primary capillary plexus where they
travel at te level of Median Eminence, via portal veins, to a secondary capillary plexus where
they stimulate the glandular tissue of the anterior pituitary to release its hormones.
 Major hormones secreted:

Hormone Other names Symbol(s) Structure Secretory cells Target Effect

Adrenocorticotropic
Corticotropin ACTH Polypeptide Corticotrophs Adrenal gland Secretion of glucocorticoids
hormone

Thyroid-stimulating Secretion of thyroid

Thyrotropin TSH Glycoprotein Thyrotrophs Thyroid gland
hormone hormones

Follicle-stimulating Growth of reproductive

- FSH Glycoprotein Gonadotrophs Gonads
hormone system

Luteinizing hormone Lutropin LH, ICSH Glycoprotein Gonadotrophs Gonads Sex hormone production

Liver, adipose Promotes growth; lipid and

Growth hormone Somatotropin GH, STH Polypeptide Somatotrophs
tissue carbohydrate metabolism

Secretion of
Lactogenic Lactotrophs and Ovaries,
Prolactin PRL Polypeptide estrogens/progesterone; milk
hormone Mammotrophs mammary glands
production
 Thyroid Stimulating Hormone (TSH):
Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a peptide hormone
synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates
the endocrine function of the thyroid gland

Regulation of thyroid hormone levels:

TSH stimulates the thyroid gland to secrete the hormones thyroxine (T4) and
triiodothyronine (T3). TSH production is controlled by thyrotropin-releasing
hormone (TRH), which is manufactured in the hypothalamus and transported to
the anterior pituitary gland via the superior hypophyseal artery, where it increases
TSH production and release. Somatostatin is also produced by the hypothalamus,
and has an opposite effect on the pituitary production of TSH, decreasing or
inhibiting its release.
The level of thyroid hormones (T3 and T4) in the
blood has an effect on the pituitary release of TSH;
when the levels of T3 and T4 are low, the production
of TSH is increased, and, on the converse, when
levels of T3 and T4 are high, TSH production is
decreased. This effect creates a regulatory negative
feedback loop.
Function of Thyroid hormones: play a vital role in cellular metabolism. The
cellular events that they mediate include the following:

• Transcription of cell membrane Na + /K + -ATPase, leading to an increase in oxygen

consumption.
• Transcription of uncoupling protein, enhancing fatty acid oxidation and heat
generation without production of adenosine triphosphate.
• Protein synthesis and degradation, contributing to growth and differentiation.

• Epinephrine-induced glycogenolysis, and insulin-induced glycogen synthesis and glucose

utilization.

• Cholesterol synthesis and low-density lipoprotein receptor regulation.

 Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH):

Luteinizing hormone:
Luteinizing hormone (LH, also known as lutropin) is a hormone produced by the anterior
pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and
development of the corpus luteum. In males, where LH had also been called interstitial
cell-stimulating hormone (ICSH), it stimulates Leydig cell production of testosterone.
LH in females:
In sexually-mature females, a surge of LH triggers the ovulation in the middle of the
cycle, stimulates the now-empty follicle to develop into the corpus luteum, which
secretes progesterone during the latter half of the menstrual cycle. Women with a severe
LH deficiency can now be treated with human LH (Luveris) produced by recombinant
DNA technology.

LH in males:
LH acts on the interstitial cells (also known as Leydig cells) of the testes stimulating
them to synthesize and secrete the male sex hormone, testosterone. LH in males is also
known as interstitial cell stimulating hormone (ICSH).
Follicle-stimulating hormone:

•Follicle-stimulating hormone (FSH) is synthesized and secreted by gonadotrophs of the

anterior pituitary gland.
•FSH regulates the development, growth, pubertal maturation, and reproductive
processes of the body.
•FSH and Luteinizing hormone (LH) act synergistically in reproduction.

FSH in females:
In sexually-mature females, FSH (assisted by LH) acts on the follicle to stimulate it to release
estrogens. FSH produced by recombinant DNA technology (Gonal-f) is available to promote
ovulation in women planning to undergo in vitro fertilization (IVF) and other forms of assisted
reproductive technology.

FSH in males:
In sexually-mature males, FSH acts on spermatogonia stimulating (with the aid of testosterone)
the production of sperm.
Adrenocorticotropic Hormone (ACTH):

•Adrenocorticotropic hormone (ACTH), also known as 'corticotropin', is a polypeptide tropic

hormone produced and secreted by the anterior pituitary gland.
•It is an important component of the hypothalamic-pituitary-adrenal axis and is often
produced in response to biological stress (along with corticotropin-releasing hormone from the
hypothalamus).
•Its principal effects are increased production and release of corticosteroids and, as its name
suggests, cortisol from the adrenal cortex.
•ACTH is cleaved into α-melanocyte-stimulating hormone (α-MSH)
Function:
•ACTH acts through the stimulation of cell surface ACTH receptors (G protein-coupled
receptor/cAMP), which are located primarily on adrenocortical cells of the adrenal
cortex. This results in the synthesis and secretion of gluco- and mineralo-corticosteroids
and androgenic steroids.

•ACTH acts at several key steps to influence the steroidogenic pathway in the adrenal
cortex:
• ACTH stimulates lipoprotein uptake into cortical cells. This increases the bio-
availability of cholesterol in the cells of the adrenal cortex.
• ACTH increases the transport of cholesterol into the mitochondria and activates its
hydrolysis.
• ACTH Stimulates cholesterol side-chain cleavage enzyme, which makes the rate-
limiting step in steroidogenesis.
 Melanocyte-stimulating hormone:

•The melanocyte-stimulating hormones (collectively referred to as MSH)

Function:
They stimulate the production and release of melanin (melanogenesis) by melanocytes in skin
and hair. MSH signals to the brain have effects on appetite and sexual arousal.

Structure of MSH:
Melanocyte-stimulating hormone belongs to a group called the melanocortins. This group
includes ACTH, alpha-MSH, beta-MSH and gamma-MSH; these peptides are all cleavage
products of a large precursor peptide called pro-opiomelanocortin (POMC). Alpha-MSH is
the most important melanocortin for pigmentation.
 Growth Hormone (GH):

Growth hormone (GH) is a protein-based peptide hormone. It stimulates growth, cell

reproduction and regeneration in humans and other animals.
•Main pathways in endocrine regulation of growth.
•Effects of growth hormone on the tissues of the body can generally be described as anabolic
(building up).
•Because polypeptide hormones are not fat-soluble, they cannot penetrate sarcolemma. GH
acts by interacting with a specific receptor on the surface of cells.
•Thus, GH exerts its effects by binding to receptors on target cells, where it activates the
MAPK pathway.
•GH stimulates the production of insulin-like growth
factor (IGF-1)
•The liver is a major target organ of GH for this process
and is the principal site of IGF-1 production.

•Additional IGF-1 is generated within target tissues,

making it what appears to be both an endocrine and an
autocrine / paracrine hormone.
 Biological Actions of Growth Hormone

GH
Adipose tissue Liver Muscle
↓ Glucose uptake
↓ Glucose uptake ↑ RNA synthesis
↑ Amino acid uptake
↑ Lipolysis ↑ Protein synthesis
↑ Protein synthesis
↑ Gluconeogenesis
↑ Somatomedin
↓ Adiposity ↑ Lean body mass

Plasma
IGFs Brain
 Bone, heart, lung Chondrocytes
 Glucose
Free fatty acids ↑ Amino acid uptake

Ketoacids ↑ Protein synthesis
↑ Protein synthesis
↑ RNA synthesis ↑ Neuronal survival
 Amino acids ↑ RNA synthesis
↑ DNA synthesis ↑ Myelin synthesis.
↑ DNA synthesis
↑ Cell size and number
↑ Collagen
↑ Chondroitin sulfate
↑ Organ size ↑ Cell size and number
↑ Organ function

 Linear growth
GH AND INSULİN
1. increases insulin resistance.
2. decreased glucose uptake in
skeletal muscle and fat tissues.
3. increased glucose production by
the liver.
4. increased insulin secretion?

– diabetogenic effect

However insulin and carbohydrates are

necessary for growth
 Prolactin (PRL):

Prolactin is a polypeptide hormone synthesized and secreted by lactotrophs in the anterior pituitary
gland.
The lactotrophs account 15%–20% of the anterior pituitary gland, increases response to elevated
estrogen levels (pregnancy).
Prolactin release is predominantly under tonic inhibition by dopamine (D2 receptor/Gi protein–
coupled receptors) derived from hypothalamic dopaminergic neurons.

Prolactin release is stimulated by sucking (decrease in the amount of dopamine released at

the median eminence), and increased levels of ovarian steroid hormones, primarily estrogen.

Prolactin receptors are found in the mammary gland, the ovary and, various regions of the brain.
 Physiologic effects of prolactin
• Development of the mammary gland, synthesis of milk, and maintenance of milk
secretion.

• Prolactin stimulates glucose and amino acid uptake and synthesis of the milk proteins
β-casein and α-lactalbumin, the milk sugar lactose, and milk fats by the mammary
epithelial cells

• During pregnancy, prolactin prepares the breast for lactation (The production and
secretion of milk is prevented during pregnancy by the high progesterone levels)

• Prolactin also modulates reproductive (inhibition of GnRH release) and parental

behavior.
DISEASES OF THE ANTERIOR PITUITARY
•Excess or deficient hormone production by the pituitary may also occur if the glands
“downstream” from it are dysfunctional. For example, under normal circumstances, the
hypothalamus detects thyroid hormone deficiency in the blood and, in response, stimulates
the pituitary to produce TSH.

•If the thyroid gland is dysfunctional and cannot produce adequate amounts, then blood
thyroid hormone levels will remain below normal even though the hypothalamus and
pituitary are promoting production..

Common Pituitary Rare Pituitary Disorders:

Disorders:
Pituitary Tumors Acromegaly and Gigantism

Growth Hormone Deficiency Cushing’s Disease

Hypopituitarism Diabetes Insipidus

Empty Sella Syndrome Nelson’s Syndrome

Kallman’s Syndrome
The most common problem with the pituitary is the development of a tumor (adenoma).
• Prolactinomas are the most common (40%–45%) pituitary tumors: elevated levels of prolactin
(hyperprolactinemia), milk secretion (galactorrhea), and reproductive dysfunction (infertility). Treated
with dopamine.
• Somatotroph (20%) adenoma: can be associated with acromegaly or bone and soft-tissue overgrowth in
adults, and with gigantism in children.
• Corticotroph (10%–12%) adenoma: associated with excess cortisol production or Cushing syndrome;
patients present with central obesity, proximal myopathy, hypertension, mood changes, dorsocervical
fat pads, and hyperglycemia.
• Gonadotroph (15%) adenoma: frequently inefficient in hormone production,
• rarely thyrotroph (1%–2%) adenoma

Whereas larger tumors can produce neurologic symptoms by mass effect in the sellar area. Blood vessels
and the optic nerves are in close proximity to the pituitary gland. Pressure from a tumor can cause headaches,
visual disturbances….
Other pituitary disorders can arise from
• Inherited genetic mutations (GH insensitivity syndrome)
• Trauma
• Impaired blood supply, due to surgical or radiation treatment of a
previous pituitary disorder.
Thank you