Anterior pituitary hormones pharmacology 2nd year bpt

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I now have comprehensive content from both Lippincott Pharmacology and Katzung's Pharmacology. Let me compile the full, well-structured answer for a 2nd year BPT student.

Anterior Pituitary Hormones - Pharmacology (2nd Year BPT)

Source: Lippincott Illustrated Reviews: Pharmacology & Katzung's Basic and Clinical Pharmacology, 16th Ed.

Overview

The pituitary gland is the "master gland." Its anterior lobe secretes 6 key hormones, all under hypothalamic control via the hypophyseal portal system. Releasing/inhibiting hormones from the hypothalamus reach the anterior pituitary and trigger synthesis and secretion of target hormones.

Anterior Pituitary Hormones and Their Targets

Important note on administration: All pituitary hormones are peptides/glycoproteins, so they are destroyed by gut proteolytic enzymes. They must be given IM, subcutaneously (SC), or intranasally - NOT orally.

Receptor Classification (Katzung)

Hormone Group	Receptor Type
GH, Prolactin	JAK/STAT superfamily
TSH, FSH, LH	G protein-coupled receptors (share α subunit; differ in β subunit)
ACTH	G protein-coupled receptor (melanocortin 2 receptor)

1. ACTH (Adrenocorticotropic Hormone / Corticotropin)

Hypothalamic control: CRH (corticotropin-releasing hormone) stimulates; cortisol provides negative feedback.

Precursor: Proopiomelanocortin (POMC) - also gives rise to α-MSH and β-endorphin.

Release pattern: Pulsatile with diurnal rhythm - highest in early morning, lowest late evening. Stress increases it.

Mechanism of Action

ACTH binds G protein-coupled receptors on the adrenal cortex → activates adenylyl cyclase → stimulates the rate-limiting step: cholesterol → pregnenolone → synthesis and release of glucocorticoids, mineralocorticoids, and adrenal androgens.

Therapeutic Uses

Diagnosis of adrenal insufficiency: differentiates primary (Addison disease - adrenal atrophy) from secondary (pituitary ACTH failure)
Cosyntropin (synthetic human ACTH, preferred over animal extract) used for the cosyntropin stimulation test
CRH used to distinguish Cushing disease from ectopic ACTH syndrome
Infantile spasms, multiple sclerosis, resistant epilepsy

Adverse Effects

Similar to glucocorticoids: hypertension, peripheral edema, hypokalemia, emotional disturbances, bone loss, increased infection risk.

2. Growth Hormone (GH / Somatotropin)

Hypothalamic control:

GHRH (growth hormone-releasing hormone) → stimulates GH
Somatostatin (SST) → inhibits GH
GH and IGF-1 → negative feedback on both GHRH and somatostatin

Release: Pulsatile; highest during deep sleep. Decreases with age.

Mechanism of Action

Direct effects: on liver, muscle, adipose tissue
Indirect effects: via IGF-1 and IGF-2 (somatomedins) produced in the liver → promote bone growth, cell proliferation, protein synthesis
GH receptors activate the JAK2/STAT5 pathway

Therapeutic Preparation

Somatropin = recombinant human GH (rhGH), made by recombinant DNA technology. Given SC or IM daily.

Clinical Uses (Approved)

Condition	Details
GH deficiency in children	Pituitary dwarfism - achieves near-normal adult height if started early
GH deficiency in adults	Reduces obesity, increases muscle mass, improves bone density
Turner syndrome	Short stature in girls
Noonan syndrome	Growth failure
Prader-Willi syndrome	Decreases body fat, increases lean mass
Chronic renal insufficiency (pre-transplant)	Growth failure
Idiopathic short stature (ISS)	Height ≥2.25 SD below normal; adds ~4-7 cm to adult height
AIDS wasting	Anabolic effect
Short bowel syndrome	Improves intestinal absorption

Adverse Effects

Injection site pain, edema, arthralgias, myalgias, nausea
Hyperglycemia (GH is diabetogenic)
Pseudotumor cerebri, slipped capital femoral epiphysis, scoliosis progression in children
Carpal tunnel syndrome in adults
Increases CYP450 enzyme activity (drug interactions)

Contraindications

Closed epiphyses (no point in treatment)
Diabetic retinopathy
Obese Prader-Willi patients with sleep apnea (risk of asphyxiation)
Active malignancy

GH Excess - Acromegaly Treatment

Somatostatin analogs: Octreotide, Lanreotide - inhibit GH release; used every 4 weeks (depot); also used for carcinoid tumors and bleeding esophageal varices
GH receptor antagonist: Pegvisomant - blocks GH signaling
Adverse effects of octreotide: bradycardia, diarrhea, gallstones (delayed gallbladder emptying), steatorrhea

3. TSH (Thyroid-Stimulating Hormone / Thyrotropin)

Hypothalamic control: TRH stimulates; T3/T4 provide negative feedback.

Structure: Glycoprotein dimer; shares α-subunit with FSH and LH; unique β-subunit confers specificity.

Mechanism of Action

TSH binds G protein-coupled receptors on thyroid follicular cells → stimulates:

Iodide uptake
Thyroglobulin synthesis
T3 and T4 synthesis and release

Pharmacological Use

Thyrotropin alfa (recombinant TSH): Used in patients post-thyroid surgery for carcinoma to stimulate radioactive iodine (131I) uptake for detecting cancer recurrence and measuring serum thyroglobulin - without stopping levothyroxine therapy

Drugs Affecting Thyroid (Related to TSH Axis)

Thioamides (propylthiouracil/PTU, methimazole): Inhibit iodination of tyrosines and coupling → reduce T3/T4 synthesis
- PTU also blocks peripheral T4→T3 conversion
- Methimazole preferred (once daily, fewer ADRs); PTU preferred in 1st trimester pregnancy
- ADRs: rash, agranulocytosis, hepatotoxicity
Radioactive iodine (131I): Destroys thyroid follicular cells; causes hypothyroidism requiring levothyroxine
Iodide (high dose - Wolff-Chaikoff effect): Transiently inhibits thyroid hormone synthesis and release; used pre-surgery and in thyroid storm

4. FSH & LH (Gonadotropins)

Hypothalamic control: GnRH (pulsatile) stimulates both FSH and LH. Continuous GnRH suppresses them.

Structure: Both are glycoprotein dimers sharing the α-subunit; distinct β-subunits.

Actions:

FSH: stimulates ovarian follicle maturation (female) and spermatogenesis (male)
LH: triggers ovulation, stimulates progesterone (female) and testosterone (male)

Gonadotropin Preparations

Drug	Source	Content	Use
Menotropins (hMG)	Urine of postmenopausal women	FSH + LH	Infertility
Urofollitropin	Urine of postmenopausal women	FSH only	Infertility
Follitropin alfa / beta	Recombinant DNA	FSH only	Infertility
hCG (human chorionic gonadotropin)	Urine of pregnant women	LH-like activity	Trigger ovulation; treat cryptorchidism
Choriogonadotropin alfa	Recombinant DNA	LH-like	ART protocols

Infertility protocol: Inject hMG or FSH for 5-12 days → follicular growth → then hCG injection → ovulation

Adverse effects: Ovarian hyperstimulation syndrome (OHSS - potentially life threatening), ovarian enlargement, multiple pregnancies.

5. GnRH and Its Analogs (Hypothalamic - controls FSH & LH)

GnRH Agonist Analogs (Continuous use = suppression)

Leuprolide, Goserelin, Nafarelin

Paradox: Continuous use downregulates GnRH receptors → suppresses FSH/LH → reduces gonadal steroids
Uses:
- Prostate cancer (medical castration)
- Endometriosis
- Precocious puberty (children)
- Suppress LH surge in ART protocols
- Uterine fibroids
Adverse effects:
- Women: hot flashes, sweating, diminished libido, depression, ovarian cysts
- Men: initial testosterone flare → bone pain; then hot flashes, edema, gynecomastia, diminished libido
- Contraindicated in pregnancy and breastfeeding

GnRH Antagonists (Immediate suppression)

Cetrorelix, Ganirelix

Block GnRH receptors directly → no initial flare
Used in ART protocols to prevent premature LH surge

6. Prolactin (PRL)

Hypothalamic control: Dopamine (from hypothalamus) tonically inhibits prolactin. TRH stimulates it. There is no specific prolactin-releasing hormone - dopamine acts as the main brake.

Physiological Roles

Stimulates and maintains lactation
Decreases sexual drive and reproductive function (inhibits GnRH)

Pharmacological Relevance

Hyperprolactinemia is the main clinical concern:

Caused by: pituitary adenoma (prolactinoma), drugs that block dopamine (antipsychotics, metoclopramide), primary hypothyroidism (high TRH stimulates prolactin)
Effects: amenorrhea, galactorrhea, infertility, loss of libido

Treatment of Hyperprolactinemia: Dopamine Agonists

Drug	Notes
Bromocriptine	Ergot alkaloid; D2 agonist; shrinks prolactinomas; 1st choice; also used in Parkinson's, acromegaly
Cabergoline	Longer acting; better tolerated; preferred over bromocriptine for prolactinoma

ADRs of dopamine agonists: Nausea, vomiting, postural hypotension, headache; cardiac valvular changes with long-term use (cabergoline).

Summary Table

Hormone	Hypothalamic Control	Receptor	Key Drug	Key Use
ACTH	CRH (+), Cortisol (-)	GPCR (MC2R)	Cosyntropin	Diagnose adrenal insufficiency
GH	GHRH (+), SST (-)	JAK/STAT	Somatropin	GH deficiency, short stature
TSH	TRH (+), T3/T4 (-)	GPCR	Thyrotropin alfa	Post-thyroid cancer surveillance
FSH/LH	GnRH (pulsatile +)	GPCR	Menotropins, hCG	Infertility, ART
Prolactin	Dopamine (-), TRH (+)	JAK/STAT	Bromocriptine, Cabergoline	Hyperprolactinemia, prolactinoma

Key Pharmacological Concept:

Pulsatile GnRH → stimulates FSH/LH (physiological)
Continuous GnRH agonist → suppresses FSH/LH (pharmacological)
Dopamine agonists → suppress prolactin (used for prolactinomas)
Somatostatin analogs → suppress GH (used for acromegaly)

Sources: Lippincott Illustrated Reviews: Pharmacology, Chapter 23; Katzung's Basic and Clinical Pharmacology 16th Ed., Chapter 37

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