Hypothalamic & Pituitary

Hormone Drugs
Side notes

• The hormones produced by the hypothalamus and

pituitary gland are key regulators of metabolism,
growth, and reproduction. Preparations of these
hormones, including products made by
recombinant DNA technology and drugs that mimic
or block their effects, are used in the treatment of a
variety of endocrine disorders
Growth Hormone
• required for normal growth during childhood and
adolescenc

• important regulator throughout life of lipid and

carbohydrate metabolism and lean body mass

• effects are primarily mediated by regulating the

production in peripheral tissues of insulin-like
growth factor 1(IGF-1).
 Growth Hormone Agonists
•Somatropin
• the recombinant form of human GH
• used for GH deficiency in children and adults
• treatment of children with genetic diseases
associated with short stature
• Turner syndrome, Noonan syndrome, Prader-Willi
syndrome

• GH treatment
• improves growth in children with failure to thrive
due to chronic renal failure or the small-for-
gestational-age condition..
 Mecasermin
• recombinant human IGF-1
• administered parenterally to children with IGF-1
deficiency.
• toxicity is hypoglycemia.
• mecasermin rinfabate
• a combination of recombinant human IGF-1 and
human insulin-like growth factor-binding protein-3
(rhIGFBP-3), which increases the half-life of IGF-1
 Growth Hormone Antagonists
• Somatostatin analogs
• a 14-amino-acid peptide, inhibits the release of GH,
glucagon, insulin, and gastrin.

•Octreotide and lanreotide

• long-acting synthetic analogs of somatostatin, are
used to treat acromegaly, carci-noid, gastrinoma,
glucagonoma, and other endocrine tumors.
• Regular octreotide--- SQ q 2–4 times
• slow-release octreotide or lanreotide IM
• - every 4 weeks for long-term therapy.
 Growth Hormone Antagonists
Pegvisomant

• a GH receptor antagonist approved for treatment of

acromegaly.

• long-acting derivative of a mutant GH that is able to

cross-link GH receptors but is incapable of inducing
the conformational changes required for receptor
activation
 Dopamine D2 receptor agonists

Bromocriptine
•are more effective at inhibiting prolactin
release than inhibiting GH release

•high doses of D2 receptor agonists have some

efficacy in the treatment of small GH-
secreting tumors.
 Prolactin Antagonists (Dopamine
D2 Receptor Agonists
Dopamine
• is the physiologic inhibitor of prolactin release.
• Prolactin-secreting adenomas usually retain their
sensitivity to dopamine.
Bromocriptinea , cabergoline, pergolide
• are effective in reducing serum prolactin
concentrations and restoring fertility.
(hyperprolactinemia)

• High doses of a dopamine agonist can also be used in

the treatment of acromegaly
Side notes

In hyperprolactinemia
• bromocriptineand other orally active D2dopamine
receptor agonists (eg, cabergoline, pergolide) are
effective in reducing serum prolactin
concentrations and restoring fertility.
Follicle-Stimulating Hormone (FSH)

Menotropins
• consist of a mixture of FSH and LH purified from
the urine of postmenopausal women
• who produce high levels of FSH and LH owing
to the disinhibition of pituitary gonadotropin
production that results from cessation of
ovarian steroidogenesis
 Follicle-Stimulating Hormone (FSH)
and its Analogs
•Three forms of FSH

1. Urofollitropin
• is a purified preparation extracted from the urine
of postmenopausal women.

2. Follitropin alpha 2 recombinant forms of

human FSH differ in
3. Follitropin beta the composition of their
carbohydrate side chains
Luteinizing Hormone, and Their Analogs
Luteinizing Hormone
• structure nearly identical to placental protein
that supports the corpus luteum during the
early stages of pregnancy
Human chorionic gonadotropin (hCG)
purified from human urine or recombinant hCG
is used commonly for an LH activity.
Lutropin
a recombinant form of human LH
Side notes

The placental protein that supports the corpus

luteum during the early stages of pregnancy, has a
structure that is nearly identical to LH and mediates
its effects through activation of LH receptors
 Gonadotropin-Releasing Hormone
and its Analogs
• is a decapeptide that stimulates gonadotropin release
when it is secreted in a pulsatile pattern by the
hypothalamus.
•Leuprolide
• was the first of a set of synthetic peptides with long-
acting GnRH agonist activity.
Other long-acting GnRH agonists
• Goserelin
• Histrelin
• Nafarelin
• Triptorelin
 Gonadotropin-Releasing Hormone
(GnRH) and its Analogs
• inhibits gonadotropin release by downregulating
GnRH receptors in the pituitary cells that normally
release gonadotropins (steady dosing in men and
women)

• used to suppress endogenous gonadotropin

secretion in women undergoing ovulation
induction with gonadotropins
Side notes
• In men and women, steady dosing with these GnRH
agonists inhibits gonadotropin release by
downregulating GnRH receptors in the pituitary
cells that normally release gonadotropins.

• In women, used to suppress endogenous

gonadotropin secretion in women undergoing
ovulation induction with gonadotropins, and
women gynecologic disorder that benefit from
ovarian suppression (eg, endometriosis, uterine
leiomyomata)
 Gonadotropin-Releasing Hormone
(GnRH) and its Analogs
• used in women with gynecologic disorder that benefit
from ovarian suppression
• endometriosis, uterine leiomyomata

• In men with advanced prostate cancer, in early

pubertal transgender adolescents
• to block endogenous puberty prior to treatment
with cross-gender gonadal hormones

• children with central precocious puberty

 Gonadotropin-Releasing Hormone
(GnRH) Antagonists
Ganirelix and cetrorelix
•used during ovulation induction in place of
GnRH agonists to suppress endogenous
gonadotropin production.

Degarelix
•approved for the treatment of advanced
prostate cancer.
 Gonadotropin-Releasing Hormone
(GnRH) Antagonists

•do not cause a tumor flare when used for

treatment of advanced prostate cancer

•less likely to cause the ovarian

hyperstimulation syndrome when used for
ovulation induction
 POSTERIOR PITUITARY
HORMONES
Oxytocin
•nonapeptide synthesized in cell bodies in the
paraventricular nuclei of the hypothalamus and
transported through the axons of these cells to
the posterior pituitary.

•effective stimulant of uterine contraction and is

used intravenously to induce or reinforce labor.
 POSTERIOR PITUITARY
HORMONES
Atosiban
•is an antagonist of the oxytocin receptor that
is used in some countries as a tocolytic

•used to treat preterm labor

Desmopressin
 Vasopressin (Antidiuretic
Hormone [ADH])
• synthesized in neuronal cell bodies in the hypothalamus and
released from nerve terminals in the posterior pituitary.
• acts through V2 receptors to increase the insertion of water
channels in the apical membranes of collecting duct cells in the
kidney and to thereby provide an antidiuretic effect.
• Extrarenal V 2-like receptors
• regulate the release of coagulation factor VIII and von Willebrand factor
(see Chapter 34).
Desmopressin

• a selective agonist of V2 receptors, is administered

orally, nasally, or parenterally in patients with
pituitary diabetes insipidus and in patients with mild
hemophilia A or von Willebrand disease.
• Vasopressin also contracts vascular smooth muscle
by activating V1 receptors.
• vasoconstrictor effect
• used to treat patients with bleeding from
esophageal varices or colon diverticula.
 Antagonists of vasopressin
receptors
Conivaptan and tolvaptan

•developed to offset the fluid retention that

results from the excessive production of
vasopressin associated with hyponatremia or
acute heart failure.