sex steroids Part 2 Flashcards
What are the 2 ways the androgen/AR complex can generate signals and describe briefly how they work
- DBD signalling –> direct gene transcription
- Non-DBD signalling –> causes signalling cascade
What are the levels of testerone during foetal, puberty, adulthood and senescence stages of life
foetal: cyclic and low production
puberty: increase in testosterone production
adulthood: starts to decline in production
what are 2 examples
Add testosterone into body for people with hypogonadism
What is oestradiol-17B
most potent oestrogen found naturally in women
what is progesterone
most important naturally occurring progestin
What are the main functions of the ovaries
- produce oocytes
- produce sex hormones oestrogen and progesterone in response to LH and FSH
(LH and FSH are pituitary gonadotrophins)
What is a single ovarian follicle composed of and what is the inner and outer layer composed of?
- a germ cell surrounded by cluster of endocrine cells organised into 2 layers separated by a basal membrane
- Inner layer surrounding oocyte: granulosa cells
- outer layers: theca cells
Outline how estriol is generated starting with estradiol
Estradiol in the liver oxidized by 17B-hypxysteroid dehydrogenase type II (17BHSD) to estrone and then to estriol
What molecule controls 17BHSD activity and therefore androstenedione production in theca cells
LH
What molecule controls CYP19 (P450arom) activity in the granulosa cells and therefore estradiol production
FSH
what does oestrogen deficiency do in boys
diminishes the pubertal growth spurt and delays skeletal maturation and epiphyseal closure so linear growth continues into adulthood
what does oestrogen do mid puberty
exerts positie feedback on GnRH secretion leading to increased LH and FSH productoin eventually leading to the begining of the menstrual cycle
What are the 2 receptor types for oestrogens
- Estrogen receptor alpha (ERa)
- estrogen receptor Beta (ERb)
what is the genomic mechanism of action for oestrogen
- enters cell by passive diffusion and binds to an ER in nucleus
- ER (inactive monomer) bound to heatshock protein 90 dissociates from it after oestrogen binds to it resulting in receptor dimerisation with hormone.
- ER dimer binds to EREs usually located in the promoter region of target genes
ERE = estrogen response elements
what is non-genomic mechanism of action for oestrogen
- interaction of hormones with oestrogen receptors located on plasma membrane of cells
- membrane localized ERs mediate the rapid activation of proteins like MAPK and rapid increase in cyclic AMP due to the hormone