Aleksandar Rašković

Pituitary and hypothalamic

hormones
 Endocrinology implies investigation of the
function of:
 hypotalamus
 pituitary hormones
 Thyroid gland
 Parathyroid gland and vitamin D
 Suprarenal glands
 Langerhans islets
 Male and female sex hormones
Pituitary and hypothalamic
hormones
According to the chemical structure
 1-steroidal hormones
- Hormones of suprarenal glands-gluco and
mineralocorticoids
- sexual hormones
- D vitamin/hormone
Pituitary and hypothalamic
hormones
- Mech action of steroidal hor.
gene-activ
- cytoplasmic receptor
 nucleus
 Regulation of gene transcription
 Synthesis of specific proteins and enzymes
 consequence
delayed onset of action;prolonged action
Pituitary and hypothalamic
hormones
 2. peptides
 Hypotalamus and pituitary gland
 Parathyroid gland
 Langerhans islets

 Thyroid hormones (bind to 3 types of

receptors - membrane, mitochondrial,
nuclear)
Pituitary and hypothalamic
hormones
 Mech of act of membrane - activ hormones
 Binding to receptors on the membrane
 adenylate cyclase, cyclic AMP
 Activation of tyrosine kinase
 Activation of serine-threonine kinase
 Phosphorylation in the cell
 consequence:
 Fast unset, short duration
Pituitary and hypothalamic
hormones
 Membrane-activ hormones
 Hypotalamus: ADH, oxytocin, gonadorelin
(GnRH), corticotrophin (CRF), protirelin
(TRF), somatostatin
 Pituitary gland: TSH, FSH, LH, GH (growth h)
 calcitonin (thyroid gland)
 Katecholamines (suprarenal gland)
 Glucagon and insulin (Langerhans islets)
Pituitary and hypothalamic
hormones
Hypothalamic h – synthesized in hypothalamus
1. indirect effect – influence on pituitary gland
secretion
2. direct effect – oxytocin, vasopressin
Gonadorelin - GnRH
indications: depend on way of administration:
1. pulsatile use- increase of secretion of LH i FSH
2. continuous release – down-regulation of GnRH
receptors – block of FSH and LH secretion
Pituitary and hypothalamic
hormones
Indication for gonadorelin-pulsatile administration

cryptorchidism – absence of one or both testes

from the scrotum
hypogonadal hypogonadism
infertility

Route of adm: sc, iv

t 1/2 10-40 min.

Side effects:
Headache, dizziness, allergic reaction
 Pituitary and hypothalamic hormones

Continuous administration of synthetic analogs of

gonadorelin

buserelin – s.c. or as a nasal spray

goserelin – s.c. (oily depot preparation)

couse down-regulation of gonadorelin receptors

inhibition of FSH and LH secretion

Th use – polycystic ovary syndrome, prostatic cancer,

breast cancer, endometriosis
Pituitary and hypothalamic hormones

side effects of goserelin and buserelin

women – menopausal effects: hot flushes,
sweating, vaginal dryness, loss of libido
men – gynecomastia, loss of libido

osteoporosis??
Pituitary and hypothalamic hormones

gonadorelin antagonists
cetrorelix, ganirelix
Th use – female infertility
m.a. – prevent of surge of LH release, but cause
release of LH in the middle of the cycle
s.c.; long t ½
s. e. – nausea, headache, reactions at injection
sites
 Pituitary and hypothalamic hormones

Somatostatin analogs - oktreotide, lanreotide

(s.c.)
Inhibit release of growth hormone
Th use:
acromegaly
endocrine benign tumors, glucagon-oma, VIP-
oma, inuslin-oma
To stop bleeding from oesophageal varices
 Pituitary and hypothalamic hormones

oxytocin: peptid, fast action

increases contractility of uterus and myoepithelial
cells of breast – milk secretion
dilation of cervix of uterus
contraction of the other parts of uterus
breast – feeding
Th use:
induction of labour
prevent of postpartal haemorrhage
nasal preparation- galactostasis (oxytocin
stimulates release of milk)
 Pituitary and hypothalamic hormones

 Vasopressin (ADH)
 cause antidiuretic (V2 receptors) and
vasospastic effect and production of VIII
coagulation (V1 rec)
 Release in case of decrease extracellular
volume and increase of osmotic pressure
Pituitary and hypothalamic
hormones
 Lack of vasopressin- diabetes insipidus-
 poliuria, polidipsia
 treatment- synthetic analog of vasopressin-
desmopresin – iv. im. in.
 lipresin, terlipresin – synthetic analog of
vasopressin with vasospastic activity
 Th use – to stop bleeding from oesophageal
varices
Pituitary and hypothalamic
hormones
 Growth hormone (GH)- peptid (191 aminoacid)
 Direct effects
 Stimulation of lipolisis
 Antagonistic effect on insulin function
 Indirect effect – anabolic effects on muscle and
bone are mediated by insulin-like growth factor
IGF-1 –somatomedin-peptids synthesized in the
liver in response to GH stimulation
 Inceased secretion of GH: acromegaly/gigantism
 Th use of GH: children with proven GH deficiency
 Pituitary and hypothalamic hormones

 Prolactin - glycoprotein- 198 aminoacids

 Stimulates growing of the breast tissue
 stimulates lactation
 Hyperprolactinaemia – oestrogen deficiency
(amenorrhoea, infertility, vaginal dryness,
galactorrhoea, osteoporosis)
 Inhibition of release:
 Dopamine
 Agonists of dopamine (bromocriptine, cabergoline-
are used to suppress prolactin secretion)
Pituitary and hypothalamic hormones

Hyperprolactinaemia

due to adenoma of pituitary gland

due to use of antipsychotic agents
Pituitary and hypothalamic hormones

FSH and LH – are stimulated by pulsatile exposure

to gonadorelin
women
FSH: follicular development
LH- rupture of the follicle, release of the ovum,
formation the corpus luteum (progesteron and
androgens)
Pregnancy – both FSH and LH like human
chorionic gonadotrophic hormone (HCG) –
produced in large quantities by the placenta
during pregnancy
 Pituitary and hypothalamic hormones

male
FSH: spermatogenesis
LH-Leydig cells- testosterone release
Gonadotrophins for the use
FSH and LH – extracted from urine (of postmenopausal
women – HMG – human menopausal gonadotrophins)
HCG – secreted by the placenta, contains large quantities of
LH
FSH alone – follitropin alfa and beta
LH alone – lutropin alfa (recombinant genetically
engineered product)
Pituitary and hypothalamic
hormones
 Indications:
 women
 infertility- first part of cycle HMG, and then
one dose of HCG for ovulation
 Male
 Stimulation of spermatogenesis
Cryptorchidism
Pituitary and hypothalamic
hormones
 Antiestrogens
 clomiphene (per os) – increase secretion of
gonadorelin and gonadotrophins
 Th use – infertility (in combination with HCG or
HMG)
 tamoxifen - carcinoma of the breast with
estrogen receptors in the tumour tissue
 raloksifen – osteoporosis – SERM – selective
estrogen receptor modulator – has estrogen-like
activity on bone