Hormones of the Ovary - 1– Oestrogen Lecture NO : 2nd MBBS Dr Muhammad Ramzan

Ovarian hormones Are the steroid hormones secreted by the ovaries, placenta that regulate the female reproductive system Major Ovarian hormones are 2 : Oestrogen and Progesterone Relaxin is another ovarian polypeptide secreted by the corpus Luteum to relax the : Cervix and pelvic ligaments during child birth WWW.thefree medical dictioary.com

Mature follicle – the histology

Oestrogen – the definition Oestrogen is one of the several steroid hormones secreted chiefly from the ovaries and placenta It promotes the development of female secondary sex characters www.merriam webster.com

Oestrogen – the background Estrogen stimulates the changes in the female reproductive organs during estrus cycle Oestrogen is also produced in Adrenal Cortex, Testis in addition to ovaries and placenta Is also present in vertebrates and insects

Oestrogen – Types and properties There are 3 major types of oestrogens in women including Estradiol E2 which is most potent and has : 10 -20% of the Oestrogen share Oestrogen is available in free and bound form Oestrogen is commonly bonded with the Steroid Binding Globulin and steroid binding albumen www.wikipedia.com

Oestradiol - Chemical structure like CH

Oestrogen – synthesis and its location Cells of Maturing Follicle Cholesterol (CH) is the primary precursor of all the steroid hormones including Oestrogen CH is abundantly available in organs where steroid genesis takes place – Gonads, Adrenal cortex and Placenta CH is first converted to Pregnenolone through Cholesterol Desmolase in the SER of the Granulosa and Theca cells of the maturing follicles

Oestrogen – the synthesis cont. Pregnenolone is altered to Progestogens and further to Androgens - Androgens are the precursor to Oestrogens in ovary - β Estradiol β - Estradiol is the active Oestrogen This reaction is catalyzed by the Aromatase with NADPH Small amount of Oestrogen is also produced by the: Placenta, Adrenal cortex and Testis

Oestrogen – the synthesis

Oestrogen- the target organs Target organs for Oestrogen are the tissues expressing Oestrogen receptors – Cytoplasmic Receptors Major target organs are the female reproductive system 1 Granulosa and Theca cells of maturing Follicle 2 Bone cells – Osteoblasts and Osteocytes (not Osteoclasts) 3 Others include : Mammary glands; CVS, immune system and CNS

Oestrogen – Regulation of secretion 2 pathways - Direct and indirect Oestrogen is regulated by 2 pathways : Neuro endocrine / indirect pathway/ Long loop Direct pathway/ Short loop/Pituitary ovarian axis

Neuroendocrine regulation/long loop pathway GnRH and GnIH It is the interaction B/W hypothalamus and circulating levels of Oestrogen - Hypothalamus – pituitary- ovarian axis Deficiency of Oestrogen stimulates the Hypothalamus to release GnRH which activates pituitary to Secrete Gonadotropins : FSH and LH . Both activate ovary to↑oestrogen Opposite is true when there is excess of Oestrogen by the secretion of GnIH from Hypothalamus (↓GnRH)

Oestrogen- Neuro endocrine regulation GnRH and GnIH

Pituitary ovarian axis Direct/short loop pathway It is the interaction B/W the circulating levels of Oestrogen and the Pituitary gland Deficiency of the serum level of oestrogen, stimulates Pituitary to  secrete Gonadotropins (FSH) which ↑ oestrogen level Opposite is true when oestrogen level is high Inhibin is a peptide hormone from the Corpus Luteum/placenta / Ovary that inhibits FSH

Oestrogen – Role of Inhibin

Estrogen – mechanism of action Formation of HRC Oestrogen has got similar mechanism of action like rest of the Steroids Estrogen is Lipophilic and diffuses into target tissues Hormone binds with the Cytoplasmic receptors to form Hormone Receptor Complex – HRC HRC increases the affinity of hormone binding at the acceptor site at the DNA strand of Nucleus

Oestrogen – mechanism of action cont. activation of Genes (HRE) HRC is translocated to the acceptor site at the DNA strand in the nucleus to form Hormone Response Element (HRE) HRE is the gene for steroids which is activated to express mRNA which leaves for cytoplasm HRE results in the transcription of mRNA which gets its exit from nucleus to cytoplasm

Estrogen – Mechanism of action conti. Receptor and Hormone is set free Translation of the mRNA leads to the synthesis of Proteins and enzymes to execute the hormonal action HRE then leaves the acceptor site at the Nucleus and releases hormone which re circulates The receptor is thus set free and can be reused

Oestrogen mechanism of action

Metabolic effects of Oestrogen – on female reproductive system and CVS and bones Major action of the estrogen is on female reproductive system, however it has variety of effects on the: CHOs , Protein and Lipid metabolism Significant effects on bones, CVS and immune system

Metabolic effects on Protein and CHO metabolism hyperglycemic/ Proteolysis Oestrogen is a weak anabolic hormone and promotes the synthesis of Steroid binding proteins - ↑Proteogenesis Reduces muscle mass by proteolysis Oestrogen reduces glucose uptake by the cells and increases blood glucose level - is hyperglycemic It increases the impaired glucose tolerance risk/test

Metabolic effects on lipid metabolism Promotes Lipogenesis Oestrogen promotes Lipogenesis, body fatty mass and redistribute it to the areas like: buttocks, thighs and breast It increases synthesis of TG and HDL- C and reduces LDL-C It reduces cardiovascular disease risk

Metabolic effects on bones – Prevents Osteoporosis Reduces Osteoclastic activities It prevents bone resorption/ osteoporosis and increases Ca deposition of bones to promotes Osteogenesis Causes earlier fusion of epiphysis in females than males Increases salts and water retention and BP

Oestrogen - Secretion abnormalities Oestrogen may be secreted in excess or there may be deficiency of Oestrogen secretion Both conditions lead to the development of important clinical conditions

Oestrogen – the deficiency Deficiency is commonly due to congenital diseases like : Pituitary failure and Hypogonadism or Polycystic ovarian syndrome – PCOS Premenupause, menopause and hysterectomy Anorexia nervosa and Extreme training /exercises

Oestrogen- excess secretion Excess may be due to Tumours of the ovaries Excessive intake of oestrogen for replacement therapy in the Menopause and hysterectomy and treatment for the : carcinoma of Breast and prostate gland