1 / 36

Steroid hormons

Steroid hormons. are chemicals released by cells Endocrine glands Higher stability. chemical messenger that transports a signal from one cell to another Paracrine Autocrine. Hormons. Hormonal cascade – amplification of signal. CNS è target cell Stimuli Action potential

eldon
Télécharger la présentation

Steroid hormons

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Steroid hormons

  2. are chemicals released by cells Endocrine glands Higher stability chemical messenger that transports a signal from one cell to another Paracrine Autocrine Hormons

  3. Hormonal cascade – amplification of signal • CNS è target cell • Stimuli • Action potential • Chemical signal • Limbic system • Hypothalamus • Pituitary gland • Target cell - hormon

  4. Hormonal cascade – feed back • t, noise, trauma • Limbic system – hypocampus • ng hypothalamic releasing hormon (corticotropin releasing hormone) • Pituitary gland receptor • Adrenocorticotrope hormon mg • (ACTH és β-lipotropin) t1/2 is longer, as t1/2 (CRH) • Adrenal cortex – zona fasciculata – receptor – cortisol - mg

  5. Various types of receptors Receptors: Peptid hormons Growth factors Aminoacid derivatives Hormons (epinephrine) Hypothetical cell Steroid hormons + receptors Nucleus Thyroid hormons + receptors Cell membrane Cytoplasm Steroid hormons Steroid receptors

  6. Biochemistry of steroid hormones • Autoradiography of Madhabananda Sar and Walter E. Stumpf • Guinea pig endometrium + radioactivly labelled progesterone (15’)

  7. Classification of steroid hormons • Sex & progestagen hormons

  8. Classification of steroid hormons • Sex & progestagen hormons

  9. Classification of steroid hormons • Sex & progestagen hormons • Hormons of adrenal cortex

  10. Cross sectional view of adrenal cortex • Cortex • Zona glomerulosa: • mineralocorticoids • Zona fasciculata: • glucocorticoids + androgens • Zona reticularis: • glucocorticoids + androgens

  11. Carbon skeleton • Cyclopentano- perhydrophenanthrene skeleton • A, B, C, D - four fused rings

  12. A koleszterin • 1.) transz, szék elnyújtott szalagszerű felépítés • 1) 3-b-OH membrán / H2O határ • 3.) 18/19 CH3, váz tömör • 4.) gátolja membrán fluiditását, gátolja a membrán befagyását • 5.) a lipoproteinek alkotórésze, szérum koncentráció – rizikótényező “A koleszterin a biológia leginkább dekorált molekulája. 13 Nobel-díjjal tüntették ki ama tudósokat, akik munkásságuk nagy részét a koleszterinnek áldozták. 1784 óta, amikor először izolálták epekövekből, szinte hipnotikus hatást gyakorolt a tudomány különböző területein dolgozó tudósokra. A koleszterin Janus-arcú molekula. Vízben való oldhatatlansága, mely hasznos a sejtmembránokban, halálhozóvá is teszi.” Michael Brown L Joseph Goldstein: Nobel Lettures 1985

  13. Stereochemistry of steroid hormons

  14. Via - D5-pregnenolonone …

  15. Reduction glucuronidization Inactivation of steroind hormones

  16. Steroid hormons - Progesterones

  17. Steroid hormons – 17ß-estradiol

  18. Steroid hormonsk – Testosteron

  19. Steroid hormons – Dehydroepiadrosteron

  20. Steroid hormons – Cortisol

  21. Steroid hormons – Aldosteron

  22. 1,25-dihydroxy vitamine D3

  23. Classification: # of C atoms • C27 • 1,25(OH)2D3 • C21 • progesteron, cortizol, aldosteron • C19 • testosteron & dehydroepiandrosteron • C18 • 17β-estradiol

  24. Steroid hormons Cholesterol C27 Pregnenolon C21

  25. Characteristic substituents • Glucocorticoids, mineralocorticoids • C11 • OH, O • Estrogens • Lack of C19 methyl groups • Ring „A” is aromatic • Steroid receptors • Estradiol Ring „A” - Rings B–C–D • Other steroid hormons other than female hormones • Ring „A” is coplanar to rings B–C–D

  26. Sterical positions of ring „A” and rings „B-C-D”

  27. Sterical positions of ring „A” and rings „B-C-D”

  28. Receptors of steroidal hormones • Hydrophobic molecules • Plasma proteins • Free diffusion • „Target cells”: receptors: in cytoplasm / nucleus

  29. Receptors of steroidal hormones • intracellular • non-steroid component • thyroid hormons • Retinoic acid • Vitamine D3 • Steroids • cytoplasmic • glucocorticoid receptors • aldosteron • nucleus – chromatin assotiated form • Other receptors

  30. Steroid Receptor Gene Superfamily

  31. Kcortisol/receptor 109 M−1 Kcortosol/CBG 107 M−1 Cortisol receptor–complex (~ 300 kDa) dimer 90 kDA heat shock protein heat shock Masking DNS-binding domain Hormon – receptor interaction - activation Hydrolysis of proteins, + charge aminoacids – DNA Ligand receptor complex translocation DNS binding site – HSE hormone response element Regulation of gen transcription Enhancement of transcription – mRNA – protein Repression – in given cases Steroid hormon receptors

  32. Biochemistry of steroidal hormones • The hormon receptor complex: • Receptor • Homodimer formation • DNS hormone response elements • Glucocortikoid RE: • 5’AGAACAnnnTGTTCT3’ • 3’TCTTGTnnnACAAGA5’ • Transcription factor: • gens

  33. Biosynthesis of steroid hormones • [cAMP]intracellulará • [Ca2+] intracellulará • [cAMP] intracellulará • Acute • Mobilisation of cholesterol – mit. membrane • Chronic • Steroidogen enzyme transcription á

  34. [cAMP]intracellulará • Cholesterol – pregnenolone • Cytochrom P450 SCC (side chain cleavage) enzyme • NADPH + H+; O2 C27 22 OH - cholesterol 22,20 diOH - cholesterol Cyt450 SCC C22

  35. [cAMP]intracellulárisá • Protein inductionStAR (Steroidogenic acut regulatory protein) • 30 kD, phosphoprotein • testis • ovary

  36. [cAMP]intracellulará • Protein induction • StAR (Steroidogenic acut regulatory protein) • Defective / non-functional StAR • Lipoid congenital adrenal hyperplasia (LCAH) • Steroid synthesis of adrenals and gonadsis lowered • Lipid deposition

More Related