1. PITUITARY HORMONES
Overview
- pituitary hormones are synthesized and secreted by the pituitary gland (“hypophysis”)
- the pituitary gland consists of 2 lobes
LOBE DESCRIPTION
ANTERIOR LOBE - consists of endocrine cells synthesizing and storing hormones
- secretion of hormones from these cells is regulated by regulatory hormones secreted by the hypothalamus and/or by blood-borne end-products of the peripheral cells that these hormones stimulate
POSTERIOR LOBE - consists of terminal axons of neurons whose cell bodies reside in the hypothalamus
- the cell bodies in the hypothalamus synthesize hormones which then are transported to the terminal axons of the posterior lobe
for storage
- secretion of hormones from these terminal axons is regulated by nervous signals originating from peripheral receptors
ANTERIOR LOBE HORMONES
Relevant Drugs
1) GROWTH HORMONE
- growth hormone (“GH”, “somatropin”) acts on GH receptors (“GHRs”) found exclusively in the liver
- stimulation of GHRs causes synthesis and secretion of insulin-like growth factor 1 (“IGF-1”) by the liver
- IGF-1 acts on IGF-1 receptors (“IGF-1Rs”) found in most cells, thus inducing growth and/or division of the stimulated cells
- consequences of IGF-1 stimulation include
TISSUE CONSEQUENCE MUSCLE - increased protein uptake
- increased protein anabolism
- decreased protein catabolism
ADIPOSE TISSUE - increased deliberation of free fatty acids
- increased beta-oxidation
MUSCLE AND ADIPOSE TISSUE - decreased glucose uptake
- decreased glycolysis
BONE - increased osteoblast activity
- decreased osteoclast activity
- regulation of GH secretion is done by 2 mechanisms
REGULATION MEDIATOR STIMULATION - growth hormone-releasinghormone (“GHRH”)
INHIBITION - dopamine (through action on D2 receptors)
- IGF-1
- 1 type
DRUG NAME DESCRIPTION SOMATROPIN General information
- recombinant GH
- administered subcutaneously
Medical uses
- treatment of turner’s syndrome
(“dwarfism”)
2) ADRENOCORTICOTROPHIC HORMONE
- adrenocorticothropic hormone (“ACTH”) acts on ACTH receptors
(“ACTHRs”) exclusively found in zona fasciculata and zona reticularis of the
adrenal cortex (see 55)
- consequences of ACTH stimulation include
TISSUE CONSEQUENCE
ZONA FASCICULATA - increased glucocorticoid synthesis and secretion
ZONA RETICULARIS - increased sex hormone synthesis and secretion
- regulation of ACTH secretion is done by 2 mechanisms
REGULATION MEDIATOR
STIMULATION - corticotropin-releasing hormone
(“CRH”)
- ADH (through action on V3 receptors, see below)
INHIBITION - glucocorticoids (mainly hydrocortisone)
- 1 type
DRUG NAME DESCRIPTION TETRACOSACTIDE General information
- synthetic analogue of ACTH
- administered intramuscularly
Medical uses
- diagnosis of adrenocortical insufficiency
3) PROLACTIN
- prolactin (“PRL”) acts on PRL receptors (“PRLRs”) exclusively found in the
mammary glands of the breasts
- consequences of PRL stimulation include
TISSUE CONSEQUENCE MAMMARY GLAND - increased milk production
(together with oestrogens, )
- upregulation of oestrogen receptors
- regulation of PRL secretion is done by 2 mechanisms
REGULATION MEDIATOR STIMULATION - prolactin-releasing hormone
(“PRH”)
INHIBITION - dopamine (through action on D2 receptors)
- 1 groupA) D2 RECEPTOR ANTAGONISTS
- D2 receptor antagonists inhibit the inhibitory action of dopamine on
PRL secretion, thus facilitating PRL secretion and following increased milk production
4) THYROID-STIMULATING HORMONE
- thyroid-stimulating hormone (“TSH”) acts on TSH receptors (“TSHRs”)
exclusively found in the follicles of the thyroid gland
- consequences of TSH stimulation include
TISSUE CONSEQUENCE
THYROID FOLLICLES - increased secretion of thyroid hormones (tetraiodotyronine and triiodothyronine)
- regulation of TSH secretion is done by 2 mechanisms
REGULATION MEDIATOR
STIMULATION - thyrotropin-releasing hormone
(“TRH”)
INHIBITION - thyroxine
- triiodothyronine
- not used clinically
5) FOLLICLE-STIMULATING HORMONE AND LUTENIZING HORMONE
- follicle-stimulating hormone (“FSH”) and lutenizing hormone (“LH”) act on
FSH receptors (“FSHRs”) and LH receptors (“LHRs”), respectively, exclusively found in the gonads
- consequences of FSH and LH stimulation may be divided in 2 groups
A) FSH STIMULATION
- consequences include
TISSUE CONSEQUENCE
OVA - development of the primordial follicles to yield mature follicles
- 4 -
- oestrogen synthesis and secretion by the mature folliclesTESTES - maturation of spermatozoa (“spermatogenesis”, together with testosterone)
B) LH STIMULATION
- consequences include
TISSUE CONSEQUENCE
OVA - rupture of the mature follicles and following ovulation
- progesterone synthesis and secretion by the remnants of the ruptured follicles (“corpus luteum”)
TESTES - testosterone synthesis and secretion
- regulation of FSH and LH secretion is done by 2 mechanisms
REGULATION MEDIATOR
STIMULATION - gonadotropin-releasing hormone
(“GnRH”)
INHIBITION - estrogen
- progesterone
- testosterone
- 1 group
A) ORAL CONTRACEPTIVES
- oral contraceptives inhibit the release of FSH and LH from the anterior
pituitary, thus preventing ovulation and following prevention of pregnancy
POSTERIOR LOBE HORMONES
- 5 -
Relevant Drugs
- 2 categories
1) ANTIDIURETIC HORMONE
- antidiuretic hormone (“ADH”, “vasopressin”) acts on ADH receptors
(“ADHRs”) found in several tissues
- there are 3 types of ADH receptors
RECEPTOR TYPE DESCRIPTION V1 Location
- vascular smooth muscle
Consequence
- vasoconstriction
V2 Location
- distal tubules and collecting ducts of the kidney
Consequence
- insertion of aquaporins in the luminal surface of the distal tubules and collecting ducts of the kidney and following sodium extretion and water reabsorption
V3 Location
- pituitary gland
Consequence
- ACTH secretion
- regulation of ADH secretion is done by 1 mechanism
REGULATION MEDIATOR
STIMULATION - stimulation of osmoreceptors in the hypothalamic capillaries by high blood osmolality
- stimulation of baroreceptors in the carotid bodies by low blood pressure
- 3 types
DRUG NAME DESCRIPTION
VASOPRESSIN General information
- ADH itself
- non-selective ADH-receptor agonist
- administered IV, intramuscularly and/or subcutaneously
Medical uses
- treatment of hemorrhagic esophageal varices
- treatment of diabetes insipidus
TERLIPRESSIN General information
- synthetic ADH analogue
- selective V1 receptor agonist
Medical uses
- treatment of hemorrhagic esophageal varices
DESMOPRESSIN General information
- synthetic ADH analogue
- selective V2 receptor agonist
- administered nasally
Medical uses
- treatment of diabetes insipidus
2) OXYTOCIN
- oxytocin acts on oxytocin receptors exclusively found in the smooth muscle cells of the uterus and surrounding the mammary glands of the breasts
- consequences of oxytocin stimulation include
TISSUE CONSEQUENCE
UTERUS - very strong rhythmic contractions leading to labor
MAMMARY GLANDS - ejection of milk
- regulation of oxytocin secretion is done by 1 mechanism
REGULATION MEDIATOR
STIMULATION - extreme distension of the uterus
(end of pregnancy)
- suckling of the nipples (breast feeding)
- 2 groups
A) OXYTOCIN RECEPTOR AGONISTS
- oxytocin receptor agonists (“oxytocic drugs”) stimulate oxytocin receptors, thus facilitating contractions of the uterus and following induction of labor
B) OXYTOCIN RECEPTOR ANTAGONISTS
- oxytocin receptor antagonists (“tocolytic drugs”) inhibit the action of
oxytocin on oxytocin receptors, thus inhibiting contractions of the uterus and following prevention of labor
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