Transcript Pituitary Gland (Hypophysis)

Pituitary Gland
Video
Endocrine System, Pituitary Gland
Anterior pituitary hormones are classified
into three families:
Somatomammotropin family (GH and PRL).
Glycoprotein hormones (LH, FSH, and TSH).
Opiomelanocortin family (ACTH, β-endorphin,
and related peptides).
Growth Hormone
(GH)
Human GH consists of 191 amino acid residues (M.W.
22,000 dalton) and contains two disulfide bridges.
GH = half-life of about 25 minutes in lean adults.
GH is inactivated mainly by the liver but also by the
kidney.
About 40% of the hormone is bound to "GH-binding
protein" (GHBP).
The GH receptors are single-membrane-bound
proteins. Each of the receptor contains an
extracellular, transmembrane, and intra-cellular
domain.
GH promotes transport and incorporation of amino
acids in skeletal muscle, cardiac muscle, adipose
tissue, and liver and is responsible for the
proportionate growth of visceral organs and lean
body mass during puberty.
GH acts directly on cartilage tissue to promote
the endochondral growth that results in
skeletal growth; however although GH has a
direct effect on chondrocyte stem cells, the
growth-promoting effect of GH is due to its
stimulation of the chondrocytes to produce
insulin-like growth factor I which then acts
locally to stimulate cellular replication in the
distal proliferative zone of the epiphyseal
plate.
GH exerts a "protein-sparing" effect by mobilizing the
body's energy substrates, such as glucose, free fatty
acids, and ketone bodies, in the same tissues in which
it stimulates protein synthesis.
GH inhibits glucose uptake by skeletal muscle by
inhibiting hexokinase activity and by desensitizing
the tissue to the actions of insulin; the effect is to
elevate the blood glucose level.
GH promotes lipolysis in adipocytes, possibly by
increasing the synthesis of hormone-sensitive lipase
(HSL), and ketogenesis in the liver.
GH increases the activity of hepatic glucose-6phosphatase, increasing glucose secretion.
These protein-sparing effects of GH are
diabetogenic and explain how GH functions as
an insulin antagonist.
GH hypersecretion in children causes increased
growth rate and can result in gigantism.
GH excess occurs infrequently in childhood, and
most frequently in middle-aged adulthood,
which leads to acromegaly (acral -- extremities
+ megas -- large), a condition in which the
cartilaginous tissues proliferate, resulting in
distorted overgrowth of the hands, feet,
mandibles, nose, brow, and cheek bones.
The major cause of GH resistance is a
genetic defect in the growth hormone
receptor (GHR) and the resultant
condition is known as Laron-type
dwarfism
Video
Endocrine System, Pituitary Gland
Prolactin
Human prolactin (PRL) contains 199 amino acid
residues (M.W. 23,500) and three intramolecular
disulfide bridges.
In healthy adults the anterior pituitary releases very
little PRL under nonstressed conditions, primarily
because PRL release is under hypothalamic inhibition.
This inhibition is exerted by dopamine or PIH.
Elevated levels of PRL stimulate milk
production in the mammary gland.
After parturition, PRL promotes milk secretion
via a neuroendocrine reflex that involves
sensory receptors in the nipples.
In mammary tissue, prolactin binds to alveolar
cells and stimulates the synthesis of milkspecific proteins (casein, lactalbumin, and
lactoglobulin) by increasing production of their
respective mRNAs.
The Opiomelanocortin Family
ACTH
ACTH is a polypeptide of 39 residues.
The first 24 of which are required for corticotropic
activity and do not vary among species.
Because (ACTH) contains the MSH sequence in
residues 6-9 (His-Phe-Arg-Trp), ACTH has intrinsic
melanocyte-stimulating activity.
ACTH can thus cause skin darkening if present in high
concentrations.
ACTH acts mainly on the cells of the zona
fasciculata of the adrenal cortex to
stimulate the synthesis and release of
cortisol.
It also stimulates the secretion of adrenal
androgens from the zona reticularis.
Binding of ACTH to receptors activates
formation of cAMP which mediates cortisol
formation and secretion and protein
synthesis.
β-Endorphin
β-Endorphin is a 31-amino-acid polypeptide
released together with ACTH.
When introduced into the third ventricle of the
brain, it produces dramatic behavioral changes,
but when injected systemically, it does not. Thus,
the function of circulating β-endorphin remains
unclear.
β-Endorphin is an agonist of the opioid
receptors, with evidence suggesting it serves as
the endogenous ligand of the μ-opioid receptor,
the same receptor to which the chemicals
extracted from opium, such as morphine, have
their analgesic and addictive effects (indeed,
the μ-opioid receptor was named based on its
most renowned ligand, morphine).
Melanocyte-stimulating hormone
(MSH)
The melanocyte-stimulating
hormones (collectively referred to
as MSH or intermedins) are a class
of peptide hormones that are produced by
cells in the intermediate lobe of
the pituitary gland.
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.
Melanocyte-stimulating hormone belongs to a
group called the melanocortins. This group
includes ACTH, alpha-melanocyte-stimulating
hormone (α-MSH), beta-melanocytestimulating hormone (β-MSH) and gammamelanocyte-stimulating hormone (γ-MSH);
these peptides are all cleavage products of a
large precursor peptide called proopiomelanocortin (POMC).
α-MSH is the most important melanocortin for
pigmentation.
Video
From Melanocyte to Melanoma
Glycoprotein Hormones
1.Thyroid-stimulating hormone
(TSH, thyrotropin)
2. Luteinizing hormone (LH) and follicle stimulating
hormone (FSH)
1. Thyroid-stimulating hormone
(TSH, thyrotropin)
TSH stimulates secretion of the thyroid
hormones T4 and T3.
TSH stimulates synthesis of thyroid hormone,
synthesis of thyroglobulin, synthesis of RNA
and protein, uptake and utilization of glucose,
and synthesis of phospholipids.
TSH action is mediated by intracellular cAMP
Release of TSH is stimulated by TRH and
inhibited by circulating T4.
T4 is converted to T3 by 5'-deiodinase.
In the normal adult, the pituitary contains
about 0.3 mg TSH, and the basal level of the
hormone in blood is about 1 ng/mL.
2. Luteinizing hormone (LH)
and follicle stimulating hormone (FSH)
LH and FSH are synthesized within the same
gonadotrophs but are products of different
genes.
They differ in carbohydrate composition (and
thus in clearance rates); although their β
subunits have the same number of amino acid
residues, they differ in amino acid sequences.
Adrenal Glands
The adrenal glands, a pair of well-vascularized
glands positioned bilaterally above the cranial
poles of the kidney, consist of two
embryologically, histologically, and functionally
distinct regions.
The outer region of each (adrenal cortex)
accounts for about 80% of the weight of
the gland and produces steroid hormones.
The inner core of each gland (adrenal
medulla) that has assumed an endocrine
function, and synthesizes and secretes
catecholamines and enkephalins.
Aldosterone
The major regulators of aldosterone secretion
are the renin-angiotensin system and
extracellular potassium ions (K+).
The renin-angiotensin system is sensitive to
changes in intravascular volume and arterial
pressure.
While potassium ions is an aldosteroneregulated substance that feeds back to reduce
aldosterone synthesis (simple negative
feedback).
Video
Renin Angiotensin Aldosterone
System RAAS Pathway, Functions &
Terms Video & Lesson Transcript |
Glucocorticoids
Cortisol (and other glucocorticoids)
promotes the conservation of glucose as
an energy source in several ways:
1. Cortisol induces and maintains the activity of
all of the specifically gluconeogenic enzymes
in the liver by increasing hepatic formation of
glucose.
2. Cortisol inhibits glucose utilization in
peripheral tissues, such as skeletal
muscle, adipose tissue, bone matrix,
lymphoid tissue, and skin, by inhibiting
glycolysis and promoting the use of
fatty acids.
This action is modulated by insulin and
thyroid hormones but is potentiated by
GH.
Cortisol promotes the liberation of fatty acids
from adipose tissue by inducing and
maintaining the synthesis of hormone-sensitive
lipase (HSL), an effect supported by GH.
11β-Hydroxysteroid
dehydrogenase
Adrenal Androgen
(Dehydroepiandrosterone (DHEA))
The zona reticularis is the innermost layer of
the cortex, about equal in size to the zona
glomerulosa in the adult.
Although there is evidence that the zona
fasciculata produces DHEA, no sulfate ester is
formed at that site; and although the zona
reticularis contains cortisol-producing cells
from the zona fasciculata, the major steroid
product of this zone is DHEAS.
Adrenal Medulla
Cells of the adrenal medulla are often referred to
as "chromaffin cells" because they contain
"chromaffin granules," electron-dense membranebound secretory vesicles with an affinity for
chromic ions (hence the name "chromaffin").
Chromaffin granules contain catecholamines
(~20%), various proteins (~35%), ATP (15%), lipids
(~20%), calcium ions, ascorbic acid, and other
substances; they are the adrenal medullary
counterparts of secretory vesicles in ganglion cells.
Phenylethanolamine-N-methyltransferase (PNMT)
Two enzymes responsible for inactivation of
catecholamines are present in most tissues but are
particularly abundant in the liver.
Catechol-O-methyltransferase (COMT) is a cytosolic,
Mg2+-dependent enzyme that catalyzes
methoxylation of catecholamines at the hydroxyl
group at position 3.
COMT utilizes S-adenosylmethionine as the methyl
donor and usually initiates inactivation.
Monoamine oxidase (MAO), a mitochondrial
enzyme that oxidizes the amino side chain of
catecholamines, acts generally (but not
invariably) on methoxylated catecholamines.
About 70% of the total output of urinary
catecholamines is 3-methoxy-4hydroxymandelic acid (also called
vanillylmandelic acid, VMA).
Video
Human Physiology - Adrenal Hormones