Buku Biokimia Harper Pdf

5/15/2019
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  • Female Reproductive HormonesBIOCHEMISTRY DEPARTMENT

  • Pituitary HormonesPosterior pituitary

    Stores and releases 2 hormones that are produced in the hypothalamus: Antidiuretic hormone (ADH/vasopressin): Oxytocin:

  • Oxytocin9 amino acid peptide, produced primarily by paraventricular nucleus and small amount by supraoptic nucleusTargets: Uterus and mammary glandsContraction of pregnant uterusStimulates contractions of the mammary gland alveoli.Milk-ejection reflex.

  • Pituitary HormonesAnterior pituitary

    Prolactin Growth Hormone (GH) Thyroid Stimulating Hormone (TSH) Adrenocorticotropic Hormone (ACTH) Follicle-stimulating Hormone (FSH) Luteinizing Hormone (LH)

  • PROLACTINProtein hormone of 199 amino acids.In females it stimulates milk production by the mammary glands. Release is inhibited in non-pregnant women. As estrogen and progesterone levels rise late in pregnancy, it stimulates prolactin release.Hyperprolactinaemia can cause menstrual problems in females and breast enlargement in males.

  • Hypo-Pit-Gonadal Axes

  • An OverviewHORMONAL CONTROL OVER GONADAL FUNCTION

  • Action of GnRHA system stimulation of phosphatidylinositol is GnRH actionGnRH binds to receptors in the cell membrane of the gonadotropePhospholipase C is activated, catalyzes the hidrolysis of PIP2 to form DAG and IP3 DAG activates protein kinase C (PKC), which phosphorylates specific proteinIt participate in the resulting secretory process to transport LH and FSH to cell exteriorIP3 stimulates of Ca2+ from calcium stroge particle, cause increased stimulation of PKCparticipates in exocytosis of LH and FSH from cell

  • Action of GnRH

  • GONADOTROPINSFollicle-stimulating hormone (FSH)

    Target: Ovaries and TestesStimulates the maturation of sperm and egg, in the females causes the release of estrogen

  • GONADOTROPINSLuteinizing Hormone (LH)

    Target: Ovaries and TestesMale: Production of testosteroneIn females works with FSH to cause follicle development, and then independently is responsible for ovulation.

  • Sex HormonesGonad and Adrenal

    EstrogenProgesteroneDihydrotestosteroneTestosterone

  • Ovarian hormones

    SteroidsEstrogensAndrogensProgesterone Peptides

  • OVARIAN STEROID HORMONES

    Produced in both interstitial and follicular cells Derivatives of cholesterol (coming from LDL-lipoproteins and de novo synthesis)

  • SYNTHESIS

  • Chemical structure: C18Source:follicular cellscorpus luteumplacentaadrenal cortexadipose tissue (DHEA androstenedione E1)

    ESTROGEN

  • SYNTHESIS First step happens in mitochondria All the rest in smooth ER Reduction in number of carbon atoms Estrogens are primarily synthesized in granulosa cells Androgens are primarily synthesized in thecal cells

  • Estrogens in circulationEstradiol Secreted by the ovaryEstrone Derived from peripheral conversion of estradiol and androstenodioneEstriol Liver metabolite of estrone

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  • ESTROGENSTransport in blood Mostly carrier-bound (albumin, sex hormone-binding globulin) Two peaks Before ovulation Mid-luteal peak Levels : much higher in the follicular fluid than in the plasma!

  • Cytoplasmic receptor binds to steroid hormone.Translocates to nucleus.DNA-binding domain binds to specific HRE of the DNA.Dimerization occurs.Process of 2 receptor units coming together at the 2 half-sites.Stimulates transcription of particular genes.

    Mechanisms of Action

  • Mechanisms of Action

  • Metabolism

    Metabolized to glucuronides and sulfates Recycled in enterohepatic circulation Excreted in urine

  • Physiological

    Reproductive system

    Development and maintenance of uterus, uterine tubes,vagina, external genitalia and breastsCyclic changes in the endometrium, cervix, vaginaGrowth of the ovarian folliclesMotility of the uterine tubes

  • Physiological

    Reproductive system

    Pregnancy: uterine muscle mass , excitability , breasts Female secondary sex characteristics (fat deposits, etc)Estrous behavior in animals, increased libido in humans

  • Physiological

    Metabolism

    Protein metabolism: anabolism- (in cattle, chicken, etc.)Lipid metabolism: LDL , plasma cholesterol Salt and water retention (by stimulating angiotensin) edema

  • Physiological

    Other metabolic

    Maintenance of bone massClotting factor synthesis ( thrombosis)

  • Progesteron

    The most distinctive hormone between males and femalesChemical structure: C21Source: c. luteum placenta follicles (small amount) adrenal cortex

  • Transport2% free80% albumin-bound18% corticosteroid-binding protein (transcortin) -bound

  • Cyclic changes in the endometrium, cervix, and vaginaBreasts: supports the secretory function during lactationInhibits LH secretionResponsible for preparing the reproductive tract for implantation and the maintenance of pregnancy

    Physiological

  • Physiological

  • OVARIAN PEPTIDE HORMONESRelaxin Relaxes pelvic joints Softens and dilates cervix Sperm mobility - in malesInhibin Selective inhibitory control of FSHActivin Selective stimulaton of FSH Cell differentiation

  • OVARIAN PEPTIDE HORMONES Follistatins Inhibit FSH secretion Gonadotropin surge attenuating factor Prevents premature LH surge POMC hormones Vasopressin and oxytocin (in luteal cells)

    ************************************

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