فارما بتيوتري گلاند

• Endocrine system


  Releases hormones into the bloodstream, which carries chemical messengers to target cells throughout the body
• Hormones


  Have a much broader range of response time than nerve impulses, requiring from seconds to days, or longer, to cause a response that may last for weeks or months
• Nerve impulses


  Generally act within milliseconds
• Hypothalamus


  Connects the nervous system with the endocrine system via the pituitary gland
• Hormones secreted by the hypothalamus and the pituitary


  • Peptides
  • Glycoproteins. both act by binding to specific receptor sites on target tissues
• Releasing/inhibiting factors or hormones


  neuropeptides produced in the hypothalamus, reach the pituitary by the hypophyseal portal system
• Hormone production


  1. Interaction of releasing hormones with receptors activates genes that promote synthesis of protein precursors

  2. Protein precursors undergo posttranslational modification to produce hormones

  3. Hormones are released into the circulation
• Each hypothalamic regulatory hormone controls the release of a specific hormone from the anterior pituitary
• Pituitary hormone preparations


  Used for specific hormonal deficiencies, but most have limited therapeutic applications
• Administration of pituitary hormones


  Intramuscularly (IM), subcutaneously, or intranasally because their peptidyl nature makes them susceptible to destruction by proteolytic enzymes of the digestive tract
• Corticotropin-releasing hormone (CRH)


  Responsible for the synthesis and release of the peptide proopiomelanocortin by the pituitary
• Adrenocorticotropic hormone (ACTH)


  Product of the posttranslational processing of the proopiomelanocortin precursor polypeptide
• ACTH


  • Normally released from the pituitary in pulses with an overriding diurnal rhythm, with the highest concentration occurring in early morning and the lowest in late evening
  • Stress stimulates its secretion, whereas cortisol acting via negative feedback suppresses its release
• Mechanism of action of ACTH


  1. ACTH binds to receptors on the surface of the adrenal cortex, activating G protein-coupled processes that ultimately stimulate the rate-limiting step in the adrenocorticosteroid synthetic pathway (cholesterol to pregnenolone)

  2. This pathway ends with the synthesis and release of adrenocorticosteroids and the adrenal androgens
• Growth hormone (somatotropin)


  • Released by the anterior pituitary in response to growth hormone (GH)-releasing hormone
  • Secretion of GH is inhibited by the hormone somatostatin
  • GH is released in a pulsatile manner, with the highest levels occurring during sleep
• Synthetic human GH (somatropin)


  Produced using recombinant DNA technology. With increasing age, GH secretion decreases, accompanied by a decrease in lean

  muscle mass. Somatotropin influences a wide variety of biochemical processes (for

  example, cell proliferation and bone growth).
• Exogenous GH


  Synthesized by gene technology and used as injection, the animal one is ineffective for human
• Effects of GH over-secretion


  • Before puberty causes Gigantism
  • After puberty causes Acromegaly
• Effects of GH reduced secretion


  • Causes Dwarfism
• Functions of GH


  • Glycogenolysis (catabolism of glycogen) -> ↑ blood sugar
  • Lipolysis (catabolism of lipid)
  • Protein synthesis
  • Increase the number of cells and their density including bone and cartilage
• Synthetic GH (somatrem)


  Has longer t1/2 = 25 min than natural GH, given to dwarf patients before puberty because after puberty the closure of long bones epiphysis occur, so administration of GH after puberty causes acromegaly, which characterized by thick skin & bone ,large nose and lower jaw and extremities

  specially fingers
• Somatostatin


  • In the pituitary, binds to receptors that suppress GH and thyroid-stimulating hormone (TSH) release
  • Also inhibits release of insulin, glucagon, and gastrin. Originally isolated from the hypothalamus,

  somatostatin is a small polypeptide found in neurons throughout the body as well

  as in the intestine, stomach, and pancreas
• Octreotide and lanreotide


  Synthetic analogs of somatostatin with longer half-lives, used in the treatment of acromegaly and severe diarrhea/flushing episodes associated with carcinoid tumors
• Gonadotropins (FSH and LH)


  Produced in the anterior pituitary, regulate gonadal steroid hormones, used in the treatment of infertility
• Menotropins (hMG)human menopausal Gonado 


  Obtained from urine of postmenopausal women, contain both FSH and LH
• Urofollitropin


  FSH obtained from postmenopausal women, devoid of LH
• Follitropin alfa and follitropin beta


  Human FSH products manufactured using recombinant DNA technology
• Human chorionic gonadotropin (hCG)


  Placental hormone excreted in urine of pregnant women, effects are essentially identical to those of LH
• Use of gonadotropins for infertility


  1. For infertile women: Menotropin at 5-12 days of menstrual cycle for growth and maturation of follicals, followed by HCG at day 13-15 from period for ovulation

  2. For infertile men: HCG for maturation of external sexual organs, followed by menotropin for induction of spermatogenesis
• Prolactin


  • Peptide hormone secreted by the anterior pituitary, primary function is to stimulate and maintain lactation
  • Also decreases sexual drive and reproductive function
• Regulation of prolactin secretion


  Thyrotropin-releasing hormone stimulates the release of prolactin, and secretion is inhibited by dopamine acting at D2 receptors
• Hormones of the posterior pituitary

  Vasopressin and oxytocin, not regulated by releasing hormones, synthesized in the hypothalamus and transported to the posterior pituitary
• Vasopressin (antidiuretic hormone)


  • Has both antidiuretic and vasopressor effects
  • In the kidney, binds to the V2 receptor to increase water permeability and reabsorption in the collecting tubules
• Oxytocin


  Used in obstetrics to stimulate uterine contraction and induce labor, also causes milk ejection by contracting the myoepithelial cells around the mammary alveoli
• Oxytocin


  • Toxicities are uncommon with proper drug use, but hypertension, uterine rupture, water retention, and fetal death may occur
  • Its antidiuretic and pressor activities are much less than those of vasopressin
• Vasopressin

  Also known as antidiuretic hormone, has both antidiuretic and vasopressor effects
• Vasopressin mechanism of action

  1. Binds to the V2 receptor to increase water permeability and reabsorption in the collecting tubules

  2. Other effects mediated by the V1 receptor, which is found in the liver, vascular smooth muscle (where it causes constriction), and other tissues
• Vasopressin

  • Major toxicities are water intoxication and hyponatremia, abdominal pain, tremor, and vertigo can also occur
• Desmopressin

  An analog of vasopressin with minimal activity at the V1 receptor, making it largely free of pressor effects, longer acting than vasopressin
• Desmopressin uses


  Preferred for the treatment of diabetes insipidus and nocturnal enuresis, administered intranasally or orally