Reproductive tutorial Flashcards
what are the 2 types of endocrine cells in the ovarian follicles and what is their function?
- thecal cells - they produce androgens in response to LH
- granulosa cells - produce estradiol in response to FSH
what are the 2 endocrine cells of the corpus luteum?
- thecal lutein cells - produce androstenedione
- granulosa lutein cells - produce estradiol and progesterone
what enzyme do the granulosa cells express?
they have high levels of the enzyme aromatase which converts androgens to estrogens
what enzyme that is present in granulosa cells is not present in thecal cells?
aromatase (ie the thecal cells canot convert androgens to estrogens)
what do high LH levels induce in the granulosa cells?
- high LH levels induce receptor upregulation and therefore increase LH responsivness in granulosa cells
What role does the 3beta-HSD-II enzyme have in the liuteal phase of the menstrual cycle?
this enzyme leads to an increased progesterone production
Describe the HPO axis in the early follicular phase
- hypothalamus secretes GnRH, which stimulates the release of FSH and LH from anterior pituitary
- LH acts on the theca cells to produce andrgens and FSH acts on the granulosa cells to produce estradiol
- the feedback inhibition of LH by estrogen is very weak, thus LH secretion remains constant or slowly increases during the follicular phase
Describe the HPO axis in late follicular phase/ ovualtion of ovarian cycle
- as progesterone is absent in this phase, the high levels of estrogen stimulate pituitary LH (but not FSH) - via positive feedback regulation - leading to the LH surge before ovulation
- estrogen also acts at the level of the hypothalamus to stimulate GnRH secretion - which accelerates pituitary LH secretion and gives a slight rise in FSH
Describe the HPO axis in the **luteal phase **of the ovarian cycle
- only when both estrogen and progesterone levels are high, is feedback inhibition of LH effective
- therefore LH levels are low in luteal phase
- the corpus luteum is dependent on LH for its survival, the falling LH leads to the diminishing of the corpus luteum - unless fertilisation and implantation occur
- therefore overall there is low estrogen, low LH, lower FSH and high progesterone
what are the 2 main types of endocrine cells in the testis & what is their function?
- sertoli cells- produce AMH, estrogen and inhibin in response to FSH
- leydig cells - produce testosterone in respone to LH
describe the** HPT axis in men**
- GnRH from the hypothalamus stimulates the secretion of FSH and LH from the pituitary gland
-
FSH acts on the sertoli cells which produce inhibin etc
* inhibin has a negative feedback effect on the FSH secretion - LH acts on the leydig cells which produce tesosterone
- the testosterone has a negative feedback effect on LH secretion
- testosterone acts on male reproductive tract and other tissues eg muscle, bone etc
what is primary hypogonadism?
- impaired gonadotrophin responsiveness eg due to FSH and LH receptor mutations
- defective androgen synthesis eg 5a reductase, 3 beta - hydroxysteroid dehydrogenase etc
- reduced testosterone and increased GnRH
what type of disorder is 5a reductase defiency?
- autosomal recessive disorder
- affects only males as DHT has no function in females
- NOTE 5a reductase converts testosterone into dihydrotestosterone
what are the charactertistics of 5a reductase deficiency?
- male gonads - high freq of crytorchidism - no fall of testes
- micropenis
- ambigious or female genitalia eg macroclitoris (hypertrophy of clitoris)
what is secondary hypogonadism?
- GnRH insufficiency
- may be due to hypopituitarisum - tumours, surgical trauma , andropause etc
- may be due to hyperprolactinemia
- may be due to congenital adrenal hyperplasa
what happens to testosterone and gonadotrophin levels in secondary hypogonadism?
- reduction in testosterone
- reduction in gonadotrophin levels
what is Kallman’s syndrome?
- inherited GnRH deficiency
- mutations in the Kal 1 gene
what do mutations of the KAL 1 gene cause?
- they interfere with** migration of GnRH secreting neurons to hypothalamus during development **
- the mutation can lead to inactivation of these genes and lead to a** greatly reduced population of GnRH secreting neurons**
- also interfere with migration of olfactory neurons to the olfactory bulb
what are the main characteristics of kallman’s syndrome?
- hypogonadotrophic hypogonadism - low GnRH and testosterone etc
- infertility
- absent / partial puvertal maturation
- 50% of cases have anosmia or hyposmia - reduced sense of smell NB distinguishing feature
what is hyperprolactinemia?
- very high levels of prolactin in the blood - can affect males and females
what are the main causes of hyperprolactinemia?
- 40% of cases due to a benign pituitary adenoma that is secreting prolactin
- other pituitary tumours that lower dopamine levels (and therefore increase prolactin levels) can also cause hyperprolactinemia
What effect does hyperprolactinemia have on gonadal function?
- it supresses LH and FSH secretion by suppressing GnRH secretion
what are the symptoms associated with hyperprolactinemia in males vsfemales
- in males, there is infertility and loss of labido
- in females there is galactorrhea and amernorrhea
what type of disorder is androgen insensitivity syndrome?
- x linked recessive disorder
- mutation in the androgen receptor gene - therefore inactivating it
what are the 3 types if androgen insensitivity syndrome?
complete - female genitalia, development of breasts, testes have not descended
partial - ambigious genitalia
mild - male genitalia, delayed puberty, sub/infertile
what are the characteristics of androgen insensitivity syndrome?
- failure of male genital development and impaired secondary sexual develoment
- wolffian structures may be absent, underdeveloped or normal
- female internal reproductive glands never present
- male gonads / testes have a high freq of cryptorchidism
how can secondary hypercortisolism (cushings) cause problems reproductivly?
- secondary hypercortisolism due to pituitary or extrapituitary excess of ACTH
- ACTH stimulates cortisol and DHEA production
- therefore there is increased negative feedback from androgens to hypothalamus and therefore less FSH and LH being secreted
- can cause amenorrhea in females and sub/infertility in males
what is congenital hyperplasia?
- a disorder of sexual development due to excess adrenal androgen secretion
what symptoms can congenital adrenal hyperplasia cause in males?
- accelerated puberty in men
- high incidence of infertility
what symptoms can congenital adrenal hyperplasia cause in women?
- ambigious genitalia
- excessive facial nhair
- menstrual irregulatory
- anoovulation- ie no ovulation
Describe sheehan’s syndrome
- due to a lot of blood loss during childbirth - which causes infarction and necrosis of pituitary gland - which can cause hypopituitarism and hypothyroidism, hypocortisolism and hypogonadotrophism
- may present immediately or may be assymptomatic for years
how is sheehans syndrome treated?
- they are given hormone replacement therapy - T4 , cortisone, gonadotrophins (if normal ovarian cycling is desired)
what is PCOS?
- most common form of chronic anoovulation in women of reproductive age
what are the clinical features of PCOS?
- hyperandrogenism - high levels of androgens
- amenorrhea / anovulation
- hirsutism - facial hair
- insulin resistance / hyperinsulinemia NB - type II diabetes
- obesity
A 25 year old woman, who was referred to the OBGYN department by her GP after complaining about not having a period for the last 6 months. she is also seeing a dermatologist for the treatment of acne and she has had 2 treatments of hair removal on her face. There is a family history of type II diabetes and obesity. Her blood shows normal FSH, high LH, high insulin, hyperglycemia, high testosterone levels , normal DHEA levels… what is the most probable diagnosis?
- PCOS
- high levels of androgens - normal FSH and high LH - points strongly to PCOS
- amenorrhea - hyperandrogenism
- high levels of glucose and insulin in the blood suggests insulin resistance - key for PCOS
- patients age also key
- family history of diabetes and obesity
do the laboratory findings for this womens blood allow us to exclude other syndromes of hyperandrogenism?
remember - high testosterone, low FSH, high LH, normal DHEA etc
- yes to some degree
- the key observation here is that normal DHEA is seen - therefore you can exclude congenital adrenal hyperplasia
- can also exclude 5a reductase defiency - only affects males
- can exclude androgen insensitivity - as she had normal ovarian cycles prior to this
