1
Q
what are the 2 types of endocrine cells in the ovarian follicles and what is their function?
A
- thecal cells - they produce androgens in response to LH
- granulosa cells - produce estradiol in response to FSH
2
Q
what are the 2 endocrine cells of the corpus luteum?
A
- thecal lutein cells - produce androstenedione
- granulosa lutein cells - produce estradiol and progesterone
3
Q
what enzyme do the granulosa cells express?
A
they have high levels of the enzyme aromatase which converts androgens to estrogens
4
Q
what enzyme that is present in granulosa cells is not present in thecal cells?
A
aromatase (ie the thecal cells canot convert androgens to estrogens)
5
Q
what do high LH levels induce in the granulosa cells?
A
- high LH levels induce receptor upregulation and therefore increase LH responsivness in granulosa cells
6
Q
What role does the 3beta-HSD-II enzyme have in the liuteal phase of the menstrual cycle?
A
this enzyme leads to an increased progesterone production
7
Q
Describe the HPO axis in the early follicular phase
A
- 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
8
Q
Describe the HPO axis in late follicular phase/ ovualtion of ovarian cycle
A
- 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
9
Q
Describe the HPO axis in the **luteal phase **of the ovarian cycle
A
- 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
10
Q
what are the 2 main types of endocrine cells in the testis & what is their function?
A
- sertoli cells- produce AMH, estrogen and inhibin in response to FSH
- leydig cells - produce testosterone in respone to LH
11
Q
describe the** HPT axis in men**
A
- 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
12
Q
what is primary hypogonadism?
A
- 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
13
Q
what type of disorder is 5a reductase defiency?
A
- autosomal recessive disorder
- affects only males as DHT has no function in females
- NOTE 5a reductase converts testosterone into dihydrotestosterone
14
Q
what are the charactertistics of 5a reductase deficiency?
A
- male gonads - high freq of crytorchidism - no fall of testes
- micropenis
- ambigious or female genitalia eg macroclitoris (hypertrophy of clitoris)
15
Q
what is secondary hypogonadism?
A
- GnRH insufficiency
- may be due to hypopituitarisum - tumours, surgical trauma , andropause etc
- may be due to hyperprolactinemia
- may be due to congenital adrenal hyperplasa
16
Q
what happens to testosterone and gonadotrophin levels in secondary hypogonadism?
A
- reduction in testosterone
- reduction in gonadotrophin levels
17
Q
what is Kallman’s syndrome?
A
- inherited GnRH deficiency
- mutations in the Kal 1 gene
18
Q
what do mutations of the KAL 1 gene cause?
A
- 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
19
Q
what are the main characteristics of kallman’s syndrome?
A
- 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
20
Q
what is hyperprolactinemia?
A
- very high levels of prolactin in the blood - can affect males and females
21
Q
what are the main causes of hyperprolactinemia?
A
- 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
22
Q
What effect does hyperprolactinemia have on gonadal function?
A
- it supresses LH and FSH secretion by suppressing GnRH secretion
23
Q
what are the symptoms associated with hyperprolactinemia in males vsfemales
A
- in males, there is infertility and loss of labido
- in females there is galactorrhea and amernorrhea
24
Q
what type of disorder is androgen insensitivity syndrome?
A
- x linked recessive disorder
- mutation in the androgen receptor gene - therefore inactivating it
25
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
26
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
27
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
28
what is congenital hyperplasia?
* a disorder of sexual development due to excess adrenal androgen secretion
29
what symptoms can congenital adrenal hyperplasia cause in males?
* accelerated puberty in men
* high incidence of infertility
30
what symptoms can congenital adrenal hyperplasia cause in women?
* ambigious genitalia
* excessive facial nhair
* menstrual irregulatory
* anoovulation- ie no ovulation
31
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
32
how is sheehans syndrome treated?
* they are given hormone replacement therapy - T4 , cortisone, gonadotrophins (if normal ovarian cycling is desired)
33
what is PCOS?
* most common form of chronic anoovulation in women of reproductive age
34
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
35
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
36
do the laboratory findings for this womens blood allow us to exclude other syndromes of hyperandrogenism?
## Footnote
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
Endocrine physiology
flashcards
Decks in class (19)
# Cards
-
Introduction to the endocrine system22
-
Hormones, receptors & hormone signalling30
-
The hypothalamus & pituitary gland30
-
The anterior lobe of the pituitary gland24
-
Hypothalamus / pituitary tutorial notes22
-
Growth hormone & insulin like growth factor17
-
thyroid gland physiology44
-
Ca2+ homeostasis47
-
thyroid & parathyroid tutorial31
-
endocrine pancreas18
-
hormone regulation of metabolism52
-
Diabetes26
-
diabetes tutorial24
-
Adrenal gland physiology56
-
adrenal tutorial22
-
Female reproductive physiology45
-
partition and lactation30
-
Male reproductive physiology29
-
Reproductive tutorial36
