Hypothalamic and Pituitary Hormones Flashcards by Maria Haslacher

Protein Hormones of the Anterior Pituitary

Placental in brackets

Somatotropic:
GH
Prolactin
(Placental Lactogen)

Glycoprotein:
   Luteinising Hormone
   Follicle Stimulating Hormone
   Thyroid Stimulating Hormone 
   (Human Chorionic Gonadotropin)

POMC- Derived Hormones
Adrenocorticotropic Hormone
Alpha Melanocyte Stimulating Hormone

How well did you know this?

Not at all

Perfectly

Regulations of GH

GH secretion increased by:
GHRH (hypothalamus)
Ghrelin (released from stomach and pancreas)

GH secretion decreased by:
Somatostatin
IGF (negative Feedback)

How well did you know this?

Not at all

Perfectly

Major Effect of GH: Direct and Indirect

Direct:
Promote bone and muscle growth
Glycolysis

Indirect through IGF:
Increased lipolysis and gluconeogenesis

How well did you know this?

Not at all

Perfectly

GH Mechanism of Action

GH–>GH-R–> JAK/STAT Pathway (incease gene express)
–> Increase IGF-1

JAK P STAT–> STAT dimerisation–> translocated to nucleus–> bind DNA–> alters expression

How well did you know this?

Not at all

Perfectly

GH Deficiency:
Causes
Symptoms
Diagnosis

Causes: Mainly hypothalamic (decrease GHRH)
Rarely pituitary injury ex irradiation

Symptoms: Pituitary Dwarfism (growth deficit in kids)
Decrease of muscle mass and increase in fat mass adults

Diagnosis: Provocative Test (insulin induced hyperglycaemia increases se GH levels)

How well did you know this?

Not at all

Perfectly

GH Deficiency Treatment
Th Options
Preparation
Formulation(s)

Th Options:
GH Analogue
GHRH Analogue- withdrawn
IGF-1- only th in Laron Dwarf or 1 deficiency in IFG-1

Preparation:
Produced in E. Coli by DNA recombinant somatotropin

Formulations:
Short Acting Injectable Solutions, daily. SC
Withdrawn: Long Acting Depot Injections (not reliable)

How well did you know this?

Not at all

Perfectly

GH Deficiency Treatment
Pharmacokinetics
Indications
Side Effects

Pharmacokinetics:
Elimination: Degradation into AA (renally)
T1/2: 30 min BUT duration of action of SC dose:
12-48hrs (due to IGF induction by drug)

Indications:
    GH Deficient Kiddies and Adults
    Chronic Renal Disease leading to growth 
          retardation in kiddies
    AIDS associated cachexia

Side Effects: Kids
Idiopathic Intracranial Hypertension; typ early SE
Scoliosis and other skeletal problems accelerated
Unknown Mech: Type 2 DM
Unknown Mech: Leukemia

Side Effects: Adults
Peripheral and Periorbital Oedema
Myalgia, Neuropathy (carpal tunnel syndrome)

How well did you know this?

Not at all

Perfectly

How to measure therapy

Initial response measured by se IGF1 levels

How well did you know this?

Not at all

Perfectly

GH Analogues

Somatropin and Somatrem

How well did you know this?

Not at all

Perfectly

GHRH Analogues

Sermorelin- Withdrawn

How well did you know this?

Not at all

Perfectly

GH Excess:
Causes
Symptoms
Diagnosis

Causes:
Micro or Macroadenoma of Pituitary

Symptoms:
Gigantism (Kiddies) and Acromegaly (Adults)

Diagnosis:
High se GH or IGF-1 Levels (glucose fails to suppress)

How well did you know this?

Not at all

Perfectly

GH Excess Treatment Options

Somatostatin Analogues
Dopamine Receptor Agonist
GH Antagonist
Non Pharmacological Option: Removal via surgery or 
    irradiation

How well did you know this?

Not at all

Perfectly

Somatostatin Analogues:
Structure
Mechanism
Effect

Structure:
Octa- or hexapeptides (longer action and more stable
than somatostatin)

Mechanism of Action:
Activate SST-R–>Gi–>decrease AC–>decrease cAMP–>
decrease hormone secretion
In Addition: via SST-R activation: K+ channels open–>
hyperpolarisation

Effects (due to hyperpolarisation and decrease cAMP and
Ca)
Inhibition of GHRH and GH release
Inhibition of secretion of TSH, insulin, VIP, carcinoid

Due to wide inhibition—> many indications for SST analogue usage

How well did you know this?

Not at all

Perfectly

Somatostatin Analogues:
Preparations
Indications
Side Effects

Preparations (using octreotide as example)
Short Acting SC Injections- T1/2: 90 min, DoA: 12hrs
Long Acting IM Injections
Slow releasing octreotide: 1x/month
Slow releasing lanreotide: 1x/2 weeks

Indications: decrease hormones or cytokines in:
Pituitary Adenoma
Thyrotrope Adenoma (overprod. TSH)
GI Tumors prod. VIP of 5HT
Th of imflammatory diseases ex IBD/RH

Side Effects:
GI Symptoms
Gall Bladder Stones
Hypothyroidism (inhib TSH secretion)

How well did you know this?

Not at all

Perfectly

Dopamine Receptor Agonists

D R Agonists decrease GH secretion in some acromegaly patients

How well did you know this?

Not at all

Perfectly

GH Antagonist
    Chemistry
    Action
    Indication
    Elimination
    Dose
    Side Effects

Chemistry:
Recombinant human GH with covalent addition of PEG
chains (–> bind to R and displace GH)
Action:
Binds to R but doesn’t activate it
Indication:
Acromegaly patients not resp to SST analogues
Elimination:
Slow due to pegylation (T1/2: 6 days)
Dose:
Loading + Maintenance
Side Effects:
Antibody Formation (uncertain relevance, may not
inhibit effect)

Somatostatin Analogues

Drug List

Octreotide

Lanreotide

Dopamine Receptor Agonists

Cabergoline

GH Antagonist

Pagvisomant

Regulation of Prolactin Secretion:
Secreted From…:
Inhibitory Reg.
Stimulators

Secreted From…:
Lactotrope Cells in Ant. Pituitary
Decidual Cells of Endometrium (Luteal and pregnancy)

Inhibitory Regulation: Dopamine
Mechanism: D2 R on Lactotropes: Gi

Stimulators:
Physiological: Breast suckling or manipulation
Non Physiological: elevated TRH

Major Effects of Prolactin

Mechanism of Prolactin Action

Th Use of Prolactin

Major Effects of Prolactin:
Breast: prep for lactation (growth and diff of mamma tis)
Other sites: Liver, Kidney, Testes, Ovaries

Mechanism of Prolactin Action:
Prolactin Receptors work like GH Receptors
JAK/STAT Pathway–> increase transcription

Th Use of Prolactin:
None

Hyperprolactinemia
Causes
Symptoms
Th Effects

Causes:
Prolactinoma (Micro or Macroadenoma Pituitary)
1 Hyperthyroidism (inc TRH), renal failure (dec TRH sec)
Drugs: cent. acting D-R Antag. and D depletors
Antipsychotics, Prokinetics, a methydopa, reserpine

Symptoms:
Gynecomastia, galactorrhea, loss of libido
Female spec: amenorrhea, anovulation
Male spec: Impotence

Th Effect:
normalisation of se prolactin levels
decrease tumor size (not curative)
normalisation: ovulation, restoration of fertility

Safe to use in pregnancy

Hyperprolactinemia
Side Effects
Other Uses

Side Effects: due to D2 R activation or 5HT R
Nausea/Vomiting (D2 and 5HT–>CTZ activation; delay
of gastric emptying)
Postural Hypotension (D2)
Digital Vasospasm (5HT2 R), Raynaud Like
CNS: psychosis, hallucinations, nightmares via 5HT2 R
Fibrosis post long term use: cor, pulmo

Other Uses:
Acromegaly: High dose D also decreases GH secretion
Parkinsons: High Dose

D2 Receptor Agonists
Mechanism of Action
Medical USe

Mechanism of Action:
   D2 R (inhibitory) (decrease AC, cAMP, PKA)
   5HT2 agonists too: not all

Medical Use:
Prolactinoma induced Hyperprolactinemia
Acromegaly: High dose D also decreases GH secretion
Parkinsons: High Dose

D2 Receptor Agonists: Ergot Derivatives Drug List

Bromocriptine T1/2: 5 hours, Bioavailability only 5% Pergolide T1/2: 27 hours Cabergoline T1/2: 65 hrs, greater D2 selectivity--> less nausea

D2 Receptor Agonists: Non Ergot Derivatives Drug List

Quinagolide Pure D2 Agonist--> no vasospasm, fibrosis T1/2: 25 hrs

Gonadotropin Releasing Hormone and Gonadotropins Regulation of Gonadotropin Secretion

GnRH: released intermittently under control of arcuate; cont admin--> desensitisation and down-regulation GnRH controls: FSH and LH secretion acts on GnRH-R on gonadotropes Gq-->PLC increase-->IP3 increase-->Ca increase Sex Steroids: Feedback Inhibiton Inhibit prod of GnRH and Gonadotropins ``` Inhibins (prod. in ovary and testes) Inhibit FSH (not LH) ```

Gonadotropins | Action and Mechanism of Action

Action: LH (and hCG) act on LH-R FSH acts of FSH-R Mechanism of Action Normal: Gs-->AC increase-->cAMP High level: Gq->PLC increase->IP3 increase->Ca increase

Effect of Gonadotropins

Men: LH: act on testicular Leydig Cells--> testosterone prod. and therefore 2ary sexual characteristics FSH: act on testicular Sertoli Cells--> spermiogenesis Females: LH: Induce ovulation (rupture of follicle) Increase progesterone synth by corpus luteum Increase androstenedion synth in theca cells FSH: Induce follicle development Increase estrogen formation in granulose cells REM: hCG has LH-like effects

Synthetic GnRH Name Usage Characteristics

Gonadorelin Usage: diagnostic purpose as so unstable T1/2: 3min used to determine cause of hypogonadism whether hypothalamic or pituitary

``` GnRH Analogues: Agonists Name Indications Mech of Action Side Effects ```

Buserelin, Goserelin Mechanism of Action: repeat admin--> desensitisation and down reg GnRH-R decrease LH and FSH secretion decrease gonadal steroid secretion-> pharma. castrat. Indications: Gonadotropin dep. precocious puberty Sex steroid dep. tumors Other sex steroid resp conditions ex endometriosis Side Effects: Transrient stimulation of tumor growth Signs of estorgen def: flush, vaginal atrophy, bone density decrease

``` GnRH Analogues: Antagonists Name Indications Mech of Action Side Effects ```

Cetrorelix, Ganirelix Indications: Sex steroid dep. tumor Suppression of LH secretion and therefore premie ovulation in FSH treated women (IVF) Mechanism of Action: Antagonist of GnRH-R--> direct pharma. castration Side Effects: HSR Signs of estrogen deficiency: flush, vaginal atrophy, bone density decrease

Use of Gonadotropins Diagnostic Uses

Diagnosis of Pregnancy: measure hCH in urine or plasma Timing of ovulation: detect LH increase in urine Diag of reproductive diseases such as: Hypogonadotropic Hypogonadism (low FSH and LH) Reduced female fertility: High FSH (sign of low estrog.)

Use of Gonadotropins Therapeutic Use: Indications

Treatment of female infertility with FSH and hCG - in vivo fertilisation to induce dev of single follicle - in vitro: to induce dev of multiple follicles Treatment of male infertility: th of gonadotropin def. Admin androgen+gonadotropin (2nd when fertility desired) ``` Treatment of cryptorchidism: induction of testicular desc. Using hCG (due to LH like effect) ```

Gonadotropin Preparations

Urinary Gonadotropins: Largely replaced by recombinant Menotropin: from urine of postmeno. females: IM Urofollitropin: highly purified FSH--> SC Recombinant Gonadotropins: Follitropin: recomb FSH Lutropin: recom LH

Ovarian Hyperstimulation Syndrome

Side Effect of Th Use of Gonatotropins FSH--> increase vascular permeability, secretion of VEGF --> decrease claudin 5 (imp. protein in tight junctions) Severe cases: not only ovaries but also ex peritoneum, thorax Th: Induce ovulation via GnRH (shorter T1/2)