Gonads 2 Flashcards
What two reactions can testosterone undergo and where?
androgens produced in gonads and adrenal glands (androstenedione is a weak precursor)
REDUCTION (5-a-reductase) - to more potent androgen
prostate, testes, seminal vesicles, skin, brain, adenohypophysis
AROMATISATION (aromatase) - oestrogen
- small amounts of testosterone produced in female adrenals as oestrogen precursor
adrenals, ovaries, liver, skin, brain, placenta
What is the more potent androgen form of testosterone?
dihydrotestosterone (DHT)
works on same androgen receptors
produced in tissue with 5-a-reductase enzyme
Describe the transport of testosterone and DHT
in the blood
60% bound to sex hormone binding globulin (SHBG)
38% albumin (binding in dynamic equilibrium)
2% free - bioactive
in seminiferous fluid
bound to androgen binding globulin
What are the actions of androgens in the foetus?
develop male internal/ex genitalia
stimulate growth (male babies larger)
behaviour
converted to oestrogens that go on to affect oestrogen receptors in the brain (and affect behaviour)
What are the actions of androgens in the adult?
spermatogenesis growth/development of male genitalia, accessory sex glands, secondary sex characteristics stimulate protein synthesis pubertal growth spurt behavioural effects feedback regulation some effects mediated by conversion to oestrogen increase sebaceous gland secretion
What are oestrogens?
any substance that induces mitosis in the endometrium
17b-oestradiol is main hormone in menstrual cycle
oestrone is precursor
oestriol is main oestrogen of pregnancy
How can oestrogens be produced?
testosterone –> oestrone to 17b-oestradiol
androstenedione –> oestrone
testosterone –> 17b-oestradiol
What are the principle actions of oestrogens?
stimulate proliferation of endometrium
final maturation of follicle
induce LH surge (for ovulation)
stimulate growth of breast ductile system
decrease sebaceous gland secretion
increase salt/water reabsorption/plasma protein synthesis
increase HDL (menopause low oestrogen so women higher risk of CVS problems)
stimulate osteoblasts
What is a progestogen?
any substance that induced secretory changes on endometrium
progesterone/17a-hydroxyprogesterone
What are the principal actions of progestogens?
stimulate secretory activity of endometrium/cervix (thick and viscous so less easily penetrated by sperm, unlike water secretions of oestrogens)
stimulate growth of alveolar system in breast
decrease renal NaCl reabsorption (competitively inhibit aldosterone)
increase body temperature
Describe the hypothalamo-pituitary-testicular axis
- neurones in hypothalamus produce GnRH in pulsatile release
- stimulates gonadotrophs in adenohypophysis to produce LH and FSH which act on testes
- sertoli cells = FSH
- leydig cells = LH
- seminiferous tubules are made of sertoli cells, where final spermatozoa processing takes place, Leydig cells between Sertoli cells
- FSH cause sertoli cells to make inhibin
- LH cause leydig cells to produce androgens
Testosterone has virilisation effects (develop male physical characteristics), direct to pituitary, indirect to hypothalamus, negative feedback (reduce amplitude of GnRH pulses)
Main negative feedback on LH production
Inhibin negative feedback to FSH axis
Summarise endocrine control of testicular function of leydig cells
Role = androgen production Stimulated by GnRH, specifically LH Reduced by negative feedback by testosterone - direct (pituitary) to reduce LH - indirect (hypo) to reduce GnRH pulse
Summarise endocrine control of testicular function of Sertoli cells
Role = spermatogenesis
Stimulated by GnRH
also requires GnRH/LH/testosterone for complete spermatogenesis
limited by inhibin (negative feedback)
What is the early follicular phase ?
BEGINNING OF MENSTRUAL CYCLE 1
oestrogen/progesterone low so little negative feedback and increase in LH, FSH, GnRH production
LH/FSH stimulate some follicles in ovaries
What is early-mid follicular phase?
2
no further increase in LH/FSH
oestrogen levels starting to rise dramatically (increases in the blood and in the ovaries - follicle produces 17b-oestradiol)
progesterone does not change
How does a local positive feedback loop in developing follicles increase oestradiol production?
- Thecal cells respond to LH by increasing androgen production
- FSH binds to receptors on granulosa cells which activates aromatase
- this converts androgens from thecal cells to 17b-oestradiol
- at start FH and LSH are high, causing a rise in oestrogen levels, oestrogens produced by granulosa cells will bind to oestrogen receptors on the same granulosa cell and stimulate aromatase enzyme by second messenger system (AUTOPOSITIVE FEEDBACK)
granulosa cells also multiply and get bigger
so more oestrogen and plasma oestrogen rises
What is the Graafian follicle?
largest follicle - no longer needs FSH to develop and proliferate
produces 17b-oestradiol
rising [] of this in absence of progesterone for min 36hrs results in negative feedback switching to positive feedback, causing the LH surge
What is the late follicular phase?
4
high oestrogen in absence of progesterone induces LH surge
LH surge overcomes FSH negative feedback so get lesser FSH surge
What is the luteal phase?
5
- after ovulation, CL forms with FSH/LH receptor cells
- oestrogen/prog falls after ovulation, FSH and LH being released stimulates CL to produce more oes/pro release
- levels rise to exert negative feedback on hypothalamo-pituitary axis
- oestrogen levels not as possible as high as in follicular stage due to high progesterone which overrides possible positive feedback
- FSH/LH decreases as they are inhibited by progesterone negative feedback
- as FSH/LH falls, corpus luteum not stimulated to make oes/pro so levels fall
- negative feedback on hypo/pit axis reduced, FSH/LH increases again
What happens if fertilisation occurs?
lots of oes/pro needed to placenta makes HUMAN CHORIONIC GONADOTROPHIN (hCG) that mimics LH action
if not fertilisation, prog/inhibin/oestradiol exert negative feedback on LH/FSH release causing luteolysis and menstruation
What is amenorrhea?
absence of menstrual cycles
primary - never happened
secondary - did happen but stopped (pregnancy)
What is oligomenorrhea?
infrequent menstrual cycle
cause due to absence of LH surge (due to insufficient oestrogenic effect at end of follicular phase)
What is infertility?
inability to get pregnant/impregante cause: physical, emotional, psychological, endocrine excess prolactin (from prolactinoma)
