development of the endocrine system prof. dr. oya ercan
TRANSCRIPT
![Page 1: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/1.jpg)
DEVELOPMENT OF THE ENDOCRINE SYSTEM
Prof. Dr. Oya Ercan
![Page 2: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/2.jpg)
Steroid hormones: are not storedrate of synthesis = rate of secretion
![Page 3: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/3.jpg)
Adrenal, gonadal steroids: Synthesis is controlled by trophic
hormones.
Stimulating hormone -------> receptor --------> activation of adenylate cyclase ------> cAMP increases
![Page 4: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/4.jpg)
• McCune Albright Syndrome: Mutation in the alpha subunit of G protein.
• Testotoxicosis: Mutation of LH receptor ( transmembrane domain - interaction with G protein.)
![Page 5: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/5.jpg)
Syndromes of hormone resistance
• Insulin resistance
• Testicular feminization
• Certain types of dwarfism
• Diabeted insipidus (nephrogenic)
• Pseudohypoparathyroidism
![Page 6: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/6.jpg)
Hormone ↑ --> receptor number decreases
• “down regulation” or “desensitization”
• obesity - insulin
• precocious puberty - GnRH analogues
![Page 7: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/7.jpg)
Hormone ↑ --> receptor number increases
• “up regulation”
• estrogen - FSH ↑ ---> LH receptors increase
![Page 8: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/8.jpg)
Distinguishing characteristic of endocrine systems: feedback control & hormone production.
![Page 9: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/9.jpg)
• The paradigm for feedback control is the interaction of the pituitary gland with the thyroid, adrenals and gonads.
• Hormones produced in peripheral endocrine organs feedback on the hypothalamic-pituitary system ------> regulate the production of the trophic hormones that control peripheral endocrine glands.
![Page 10: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/10.jpg)
All hormones are under some type of feedback control:
by cations (Ca-PTH)by metabolism (glucose-insulin)by other hormonesby osmolality or extracellular fluid volume
(vasopressin)
![Page 11: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/11.jpg)
Direct Negative Feedback
• Metabolite
• Cortisol --> ACTH
• Thyroid hormones --> TSH
![Page 12: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/12.jpg)
Indirect Negative Feedback
• Cortisol --> CRF (corticotropin releasing factor)
• Thyroid hormones --> TRH
![Page 13: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/13.jpg)
Short Feedback
• TSH --> TRH
• ACTH --> CRH
![Page 14: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/14.jpg)
Positive Feedback
• Hypophysogonadal (only example) : Estrogen --> LH, FSH
![Page 15: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/15.jpg)
Fetal Zone• CYP17 (p450c17) --> DHEA --> placental estrone,
estradiol --> DHEAS --> placental estriol
• Sulfotransferase
Transitional Zone• CYP17 + 3β HSD --> cortisol
Outer Definitive Zone• 3β HSD --> mineralocorticoids
![Page 16: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/16.jpg)
Fetal cortisol --> cortisone(Midgestation: cortisone (x4-5 cortisol))
• Cortisone: relatively inactive glucocorticoid; it protects the anabolic milieu of the fetus: cortisol can retard placental and fetal growth.
• As term approaches; liver, lung express 11-ketosteroid reductase activity:
cortisone --> cortisol• Cortisol: an important stimulus for preparing the
fetus for extrauterine survival.
![Page 17: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/17.jpg)
Insulin-like Growth Factors (Somatomedins)
They mediate growth promoting action of GH.• GH is the primary regulator of their plasma
level.• They all have insulin-like activity.• They are mitogenic for
chondrocytes,osteoblasts and a variety of cells derived from extraskeletal tissues.
• They are transported in plasma bound to carrier proteins → their half life is extended.
![Page 18: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/18.jpg)
Biological Effects
• In adipose tissue, IGF’s have the same metabolic actions as insulin but are 1/16th as potent. They stimulate chondrocyte DNA,RNA,protein,collagen and proteoglycan synthesis.
• They act primarily on the skeletal tissues but also stimulate a wide variety of extraskeletal tissues to grow and differentiate.They induce hypoglycemia; on a molar basis IGF-1 is about 1/16th as potent as insulin in producing hypoglycemia.
Endocrine,paracrine,autocrine actions. Growth promoting effects through IGF
receptors;metabolic effects through insulin receptors.
![Page 19: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/19.jpg)
• IGF-1 is lowest at birth and rises progressively throughout childhood.After puberty,plasma IGF level falls to normal adult values.
• The major regulator of IGF-1 level in serum after birth is GH. Nutritional status is also very important (Malnutrition→IGF↓). There is a decline of about 30% during sleep (sleep associated secretion of GH?).
![Page 20: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/20.jpg)
IGFBPs
IGFBP-1 = 27500 dalton
GH, IGF-1→upregulate IGFBP3
↘downregulate IGFBP1
![Page 21: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/21.jpg)
• The morning IGFBP-1(peak levels during the night and a nadir during the day) levels are age-dependent.
• During childhood,a significant inverse relation is found between IGFBP-1 concentration and chronological age.
• This pattern is the opposite of that found for total IGF-1 and for IGFBP-3.IGFBP-1 may act as a transport protein for IGF-1 and IGF-2 from the circulation to their target cells.
![Page 22: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/22.jpg)
• IGFBP-3 in the circulation have been proposed to assure a constant supply of IGFs from a storage pool.Furthermore,BP-3 prevents the insulin-like action of IGFs and protects against hypoglycemia.
• The levels of circulation IGFBP-3 in healthy subjects show an age-dependent pattern similar to that reported for IGF-1. IGFBP-3 level is equimolar with the total IGF-1 plus IGF-2 concentration suggesting that all IGFBP-3 in circulation is saturated with IGF-3.
• The levels are decreased in GH deficiency.
![Page 23: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/23.jpg)
![Page 24: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/24.jpg)
![Page 25: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/25.jpg)
![Page 26: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/26.jpg)
![Page 27: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/27.jpg)
![Page 28: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/28.jpg)
![Page 29: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/29.jpg)
![Page 30: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/30.jpg)
![Page 31: DEVELOPMENT OF THE ENDOCRINE SYSTEM Prof. Dr. Oya Ercan](https://reader036.vdocuments.us/reader036/viewer/2022062423/5697c0021a28abf838cc34f0/html5/thumbnails/31.jpg)
FETAL ZONE
• CYP 17 (p450c17) DHEA , DHEAS• Sulfotransferase Placenta Placenta estrone estriol estradiol