Male and Female Reproduction Flashcards
What two types of cells are found in the testes?
- Leydig cells
2. Sertoli cells
What kind of cells are leydig cells and what do they secrete?
- they are interstitial cells (major endocrine tissue)
- they secrete testosterone
Where are sertoli cells located and what are their functions?
- part of seminiferous tubules
1. spermatogenesis
2. form blood-testis barrier
3. secrete androgen-binding protein
What does androgen-binding protein do?
facilitates spermatogenesis
How is testosterone, estradiol and dihydrotestosterone synthesized (major pathway)?
- Cholesterol
- Pregnenolone
- 17 alpha-hydroxypregenolone by 17 alpha-hydroxylase
- dehydroepiandrosterone
- androstenediol
- testosterone
- a) estradiol by aromatase
- b) dihydrotestosterone by 5 alpha-reductase
How is testosterone synthesized (minor pathway)
- Cholesterol
- pregnenolone
- progesterone
- hydroxyprogesterone by 17 alpha-hydroxylase
- androstenedione
- testosterone
What is dihydrotestosterone?
a more potent androgen than testosterone
What is the pathway that makes estradiol without testosterone?
- cholesterol
- 17 alpha-hydroxypregnenolone
- dehydroepiandrosterone
- androstenedione
- estrone
- estradiol
What is the testosterone axis?
- gonadotropin releasing hormone (hypothalamus)
- luteinizing hormone (pituitary)
- testosterone (leydig cells in testes)
What are testosterone’s functions?
- normal spermatogenesis
- secondary sexual characteristics
- anabolic effects on muscle, liver and kidney
What do testosterone levels in blood depend on?
- steroidogenic abilities of individual Leydig cells
- total number of Leydig cells per testes
- luteinizing hormone levels
In the blood, what is testosterone bound to?
- albumin (38%)
- or sex hormone binding globulin (60%)
Where is sex hormone binding globulin synthesized?
in the liver
What is testosterones action on target cells?
- circulates bound
- enters cell once free
- is reduced to dihydrotestosterone by 5 alpha-reductase or aromatized to estradiol
What type of enzyme is aromatase?
it is a cytP450 type enzyme
How can aromatase be upregulated?
upregulated by EDC (endocrine disrupting chemicals)
What do testosterone and dihydroxytestosterone have in common?
they bind the same receptor
How are leydig cells involved in the Hyp-Pit-Testicular Axis?
- luteinizing hormone binds luteinizing hormone receptor
- adenylyl cyclase increased
- cAMP increased
- StAR increased
- testosterone syntheis and release stimulated
What gives feedback for the leydig cells involved in the Hyp-Pit-Testicular Axis?
- Negative feedback from estradiol and testosterone
2. positive feedback by activin to increase follicle stimulating hormone
How are the sertoli cells involved in the Hyp-Pit-Testicular Axis?
- Follicle stimulating hormone binds follicle stimulating hormone receptor
- adenylyl cyclase increased
- cAMP increased
- androgen-binding protein increased
- increase in concentration of intratubular testosterone
What gives feedback for the sertoli cells in the Hyp-Pit-Testicular axis?
- Negative feedback by testosterone, dihydroxytestosterone, estradiol, and inhibin to decrease follicle stimulating hormone
What receptor is used by luteinizing hormone and follicle stimulating hormone?
GPCR Galpha s
What family are inhibin and activin in?
TGF-beta (transforming growth factor) with mullerian inhibiting factor
What is inhibin’s function?
inhibits follicle stimulating hormone secretion from the pituitary
Where is inhibin produced?
produced by the sertoli cells (male) late granulosa (inhibin B) and corpus luteum (inhibin A) (female)
What is inhibin made up of?
heterodimers of alpha and beta subunit
What is activin’s function?
activates follicle stimulating secretion and binding
Where is activin produced?
produced by leydig cells (male) early granulosa cells or late corpus luteum (female)
What is activin made up of?
hetero and homodimers of beta subunits
What is the function of follistatin?
binds activin, decreases bioavailability, and decrease follicle stimulating hormone synthesis
What two types of cells are present in the ovaries?
- Granulosa cells
2. Theca cells
What is produced in the granulosa cells?
- estradiol (has aromatase)
- activin
- granulosa-lutein (in luteal phase)
- progesterone
- inhibin
What is not produced in the granulosa cells and why?
- androgens are not produced here because there is no 17 alpha-hydroxylase
- also lacks luteinizing hormone receptor
What is produced in the theca cells?
androstenedione (has 17 alpha-hydroxylase)
What is not produced in the theca cells and why?
- estradiol is not made here because theca cells lack aromatase
- there are also no follicle stimulating hormone receptors
What does estrogen do to the body?
produces secondary sex characteristics, stimulates the uterus and ovary size and development
What acts to synthesize in granulosa cells and in theca cells?
- granulosa cells: follicle stimulating hormone
- theca cells: luteinizing hormone
What is SF-1?
- steroidogenic factor 1
What is StAR?
- steroidogenic acute regulatory protein
What changes in the corpus luteum part of the two cell hypothesis?
- luteinizing hormone now acts to synthesis progesterone in the granulosa cells
What are the three phases in the menstrual cycle regulation?
- Follicular phase
- Luteal phase
- Cessation
What stimulates expression of follicle stimulating hormone and luteinizing hormone?
- hypothalamic release of gonadtropin releasing hormone
What does estradiol do to the brain?
increases the sensitivity of the the pituitary to gonadtropin releasing hormone
What happens with gonadotropin releasing hormone in the follicular phase?
- initially a slow pulse frequency
- stimulates follicle stimulating hormone (favoured if increase in activin) and luteinizin hormone
What happens with follicle stimulating hormone in the follicular phase?
- increase in estradiol from granulosa cells
-
What does the increase in estradiol from follicle stimulating hormone in the follicular phase cause?
- provides negative feedback to the hypothalamus and pituitary
- initially decrease in amount of gonadotropin releasing hormone
- later results in increased gonadotropin releasing hormone pulse frequency
- decrease follicle stimulating hormone relative to luteinizing hormone
What happens with insulin-like growth factors during the follicular phase?
enhance response to follicle stimulating hormone
What happens with luteinizing hormone during the follicular phase?
- increase in estradiol
- increase sensitivity of pituitary to gonadotropin releasing hormone
- increase in luteinizing hormone
- ovulation
What happens during the luteal phase?
- increase in progesterone (negative feedback on gonadotropin releasing hormone
- increase inhibin A (decreases follicle stimulating hormone)
- later, higher luteinizing levels (relative)which increases activin and increases follicle stimulating hormone to restart cycle
What happens during cessation (no implant)?
- luteolysis
- decrease in estradiol, progesterone, and inhibin (luteinizing hormone receptor down regulation in folicular cells)
What causes menstruation during cessation?
prostaglandins cause vasoconstriction and relaxation resulting in menstruation
What is the cycle driven by?
- alterations in gonadotropin releasing hormone pulsation which favor the production of different gonadotropins
What does follicular development result in?
- estradiol production
- then causes positive feedback to produce luteinizing hormone surge
After ovulation, what does the corpus luteum produce?
- produces progesterone
- causes slowing of gonadtropin releasing hormone pulse and decrease in luteinizing hormone
What is essential for the maintenance of the menstrual cycle?
- the characteristic periodic secretion of gonadotropin releasing hormone from the hypothalamus at an average rate of one pulse an hour
What causes the pulses of gonadotropin releasing hormone?
- oscillations in the electrical activity of the gonadotropin releasing hormone pulse generator
What influences the gonadotropin releasing hormone pulse generator?
- assortment of interactions of multiple neural, hormonal and environmental inputs to the hypothalamus
- conditions like stress, light changes, exercises and sleep
- specific metabolic signals meant for energy homeostasis
What is tightly regulated for maintenance of reproductive cycles as well as an intrinsic property of gonadotropin releasing hormone cells?
- pulsatile gonadotropin releasing hormone release
What do gonadotropin releasing hormone neurons exhibit?
spontaneous action potentials that are associated with Ca2+ oscillations and hormone secretion
What appears to stimulate gonadotropin releasing hormone release and how?
- increased cAMP levels in neurons by activation of cAMP-gated cation channels (cyclic nucleotide-gated ion channels)
What does the activation of cyclic nucleotide-gated ion channels correlate with?
- increased neuronal excitability and calcium oscillations
How are these cAMP levels potentially decreased?
- potential negative feedback pathways by inhibiting adenylyl cyclase V and activating a phosphodiesterase
Why must gonadotropin-releasing hormone be pulsatile?
- if not pulsatile then luteinizin hormone ad follicle stimulating hormone becomes desensitized
