• Anterior Pituitary Hormone that is regulated by Hypothalamic release of Growth hormone-releasing hormone (GHRH) (+) stimulates, and Somatostatin (-) inhibits.
• Target Organ(s) of GH are Liver, muscle, bone, kidney and others.
• Primary Target Organ Hormone or Mediator: Insulin-like growth factor-1 (IGF-1).
• Act through JAK/STAT receptors.

• Anterior Pituitary Hormone.
• Hypothalamic regulation by Thyrotropin-releasing hormone (TRH) stimulates (+).
• Target Organ: Thyroid.
• Primary Target Organ Hormone or Mediator: Thyroxine, triiodothyronine.
• Act through G protein-coupled receptors.

• Anterior Pituitary Hormone that is regulated by Hypothalamic release of Corticotropin-releasing hormone (CRH) stimulates (+).
• Target Organ: Adrenal cortex.
• Primary Target Organ Hormone or Mediator: Glucocorticoids, mineralocorticoids, androgens.
• Act through G Protein-coupled receptors.

• Anterior Pituitary Hormone that is regulated by hypothalamic release of Gonadotropin releasing hormone (GnRH) (+) endogenous release in pulses stimulate; (-) When given continuously as a drug, GnRH and it's analogs inhibit.
• Target Organ: Gonads.
• Primary Target Organ Hormone or Mediator: Estrogen, progesterone, testosterone.
• Act through G protein-coupled receptors

• Anterior Pituitary Hormone that is regulated by hypothalamic release of Gonadotropin releasing hormone (GnRH) (+) endogenous released in pulsed stimulate (-) When given continuously as a drug, GnRH and it's analogs inhibit.
• Target Organ: Gonads.
• Primary Target Organ Hormone or Mediator: Estrogen, progesterone, testosterone.
• Act through G protein-coupled receptors.

• Anterior Pituitary hormone regulated by Hypothalamic release of Dopamine (-) inhibitory.
• Target Organ: Breast.
• Act through JAK/STAT receptors.

Synthetic Oxytocin-injection

Oxytocin Citrate-buccal route or nasal spray

• Uses: Induce or support labor, stimulate milk ejection, induce abortion.
• Side Effects: Uterine Rupture.
• Contraindications: Abnormal fetal position, previous uterine surgery, fetal distress. 

• Uses: (Regimen to be established)-Increase Growth in children with GH insensitivity and low IGF-1 levels.

GH Receptor Antagonist

(Pegrisomant)

• Uses: Decrease IGF-1 in acromegaly.
• MOA: Decrease GH effects by preventing GH from stimulating IGF-1 production. 

Synthetic GHRH

(Seromorelin)

• Uses: Dwarfism; Short Stature (GH deficiency)
• Less effective then GH, but less expensive.
• MOA: Increases GH production. 

Octreotide

(Somatostatin Analog)

Bromocriptine

(Parlodel)

• Orally effective dopinergic agonist.

1. Via D2 is a TRH inhibitor.
2. Via D1 stimulates dopamine.

• Uses: Hyperprolactinemia, suppression of normal lactation.
• Side effects: Nausea, Vomiting, postural hypotension.
• Dosage:2.5mg and 5mg capsules, increase weekly. Initiate at 1.25mg QD-BID MDD 15mg.

• Stimulates lactation
• Increase prolactin which in turn increases milk production.
• Dopamine (D2) receptor antagonist.
• Increase TRH==>(+) stimulates Prolactin

Recombinant DNA

(Serostim, Genotropin)

• Uses:Treatment of pituitary dwarfism; Short stature (Children); GH-deficient adults
• Short plasma T¹/2 (~20 minutes) but longer biological T¹/₂ (9-17 hours)- dosing based upon IGF-1 levels may increase efficacy.
• Increases GH levels. 

Cabergoline

(Dostinex)

• Uses: Maybe useful in Prolactinomas resistant to Bromacriptine therapy. 
• 0.5mg tabs
• Initiate at 0.25mg twice weekly, MDD 1mg twice weekly. 

Cromocriptine, Pergolide, Cabergoline

(Dopamine Agonists)

What could be an indication for all these drugs?

• Uses: Decrease GH secretion in acromegaly

Diagnosing Hyperprolactinemia

What are normal levels?

• Normal levels: 15-25ng/mL
• Hyperprolactinemia levels: >30ng/mL
• Modest elevations: 30-100ng/mL:

1.  
   1. Pregnancy, Stress, Hypothyroidism, Kidney failure, Liver Failure, Medications, "Stalk effect", Other.

• Drug Induced (Typically <100ng/mL)
  • Dopamine Antagonists
    • Phenothiazines
    • TCA's
    • Metoclopramide
  • Verapamil
  • SSRI's
  • Estrogen/Progesterone
  • Methyldopa
• Levels >200ng/mL are adenomas

G Protein-Coupled Receptors (GPCR)

Mechanism

1. Extracellular N-terminus of the 7-TM protein has a ligand bound to the extracellular domain.
2. This causes a conformational change which causes the G protein bound domain to the intracellular C-terminus to replace it's GDP bound in it's inactive phase with a GTP to activate the GPCR.
3. The activated G protein then activates adenylate cyclase which causes enzymatic reactions which will cause the effect.
4. The G-GTP protein must then be hydrolyzed in order to return to it's inactive state of G-GDP.

 [image]

Type of acidophils of the adenohypophysis (anterior pituitary) that secretes growth hormone, and somatotropin. "somato" pre-fix means body so hormone associated with regulation of size of the body."

• A type of basophil found in the adenohypophysis "anterior pituitary" TSH. "Thyro" pre-fix is clearly indicating thyroid. 

Basophillic cells in the anterior pituitary that produce adrenocorticotropic hormone (ACTH) "Cortico" prefix automatically think steroids.

A basophillic cell of the anterior pituitary specialized to secrete FSH and LH. "Gonado" Think Gonads and therefore sex hormones. 

Are cells in the anterior pituitary that produce prolactin. "Mammo" think mammary of some preggerz chick. 

Endocrine Drugs

What are the three major functions they can have?

1. Replacement Therapy
2. Antagonists to treat conditions caused by excess production of hormones.
3. Diagnostic tools for identifying endocrine abnormalities. 

• Uses: For treatment of sever IGF-1 deficiency unresponsive to GH.
• Mecasermin is a complex of recombinant human IGF-1 (rhIGF-1) and recombinant human insulin-like growth factor-binding protein-3 (rhIGFBP-3). The binding protein is important in order to maintain an adequate half-life of rhIGF-1.
• Most Common side effect is hypoglycemia take a meal or snack w/i 20 minute window of dose to prevent this. 

• An Oxytocin Antagonist of the receptor which is used to treat pre-term labor.

• In women: FSH is responsible for  directing follicle development.
• In Men: FSH is the primary regulator of spermatogenesis.
  • FSH helps maintain high local androgen concentrations in the vicinity of developing sperm by stimulating the production of androgen-binding protein (ABP) by Sertolli cells. 
  • FSH stimulates the conversion by Sertolli cells of testosterone to estrogen.
• LH is the main stimulus for the production of testosterone by Leydig cells.