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Pharmacology PED1003 > Endocrine pharmacology: Female sex hormones > Flashcards

Endocrine pharmacology: Female sex hormones Flashcards

1
Q

Types of female sex hormones

A

Oestrogen
Progesterone
Androgen

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2
Q

Oestrogen: Fertility

A

Growth of ovarian follicles
Endometrial growth
Increase in tubal motility and uterine contractions

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3
Q

Oestrogen: Lactation

A

Stimulation of duct growth

Inhibits milk let-down (prolactin)

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4
Q

Oestrogen: Secondary sexual characteristics

A 
Breast development
Female habitus (Skeletal, skin, metabolism)
Development of external genitalia
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5
Q

Progesterone: Fertility

A

Endometrial receptivity
Decrease in fallopian tube motility
Decrease in uterine contractions

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6
Q

Progesterone: Lactation

A

Stimulation of lobuloalveolar development

Inhibits milk let-down (prolactin)

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7
Q

Progesterone: PMS

A

Progesterone withdrawal

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8
Q

Hypothalamic-pituitary-ovarian axis

A

GnRH pulsatile generator is in the arcuate nucleus of the hypothalamus.
GnRH is released into blood stream and travels to anterior pituitary gland.
Anterior pituitary releases FSH and LH.
FSH and LH bind receptors on different target cells in the ovary to release either aoestrogen or progesterone, respectively.

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9
Q

In ovary - FSH

A

Granulosa cells of the Graafian follicle = Oestrogen

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10
Q

In ovary - LH

A

Corpus luteum - differentiated granulosa and invasive theca cells = Progesterone and Oestrogen

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11
Q

GnRH

A

Gonadotropin-Releasing Hormone

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12
Q

FSH

A

Follicle Stimulating Hormone

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13
Q

LH

A

Leutinizing Hormone

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14
Q

Ovarian steroidogenesis

A

Two main pathways (Δ4 and Δ5)
Estradiol and estrone are oestrogen
Pathway depends on tissue type and is influenced by which enzymes are present.

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15
Q

The Ovarian Cycle - Follicular phase

A
  1. FSH is increasing due to low ovarian hormone production.
  2. FSH aids follicular development.
  3. Follicles produce oestrogen.
  4. High concentration of oestrogen >48 hours
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16
Q

The Ovarian Cycle - Ovulation

A
  1. Positive feedback from increased oestrogen initiates the LH surge.
  2. The LH surge induces ovulation
  3. The remainder of the ovulation follicle because luteinised (CL formation)
  4. It secretes progesterone and oestrogen (CL in bloom)
  5. If not pregnant then CL regresses and there’s a decrease of oestrogen and progesterone.
17
Q

Fate of the corpus luteum

A

Produces progesterone and oestrogen. Preparing the uterine lining endometrium for implantation and pregnancy.
Programmed to be steroidogenic for 14 days unless pregnant.
If pregnant the CL remains until the placenta takes over steroidogenesis at week 13 of gestation.
Corpus luteum means ‘yellow body’

18
Q

If no fertilisation

A

Decrease in progesterone and oestrogen.
Corpus luteum regression progesterone and oestrogen levels drop.
Endometrium can not be maintained, menstruation occurs.
LAck of progesterone also means the clamp on GRH, FSH and LH secretion is released.
These hormones are secreted again, cycle starts again, follicle development.

19
Q

Fertilisation and implantation

A

Ovum secretes human chorionic gonadotrophin (HCG), this stimulates corpud luteum to continue secreting progesterone.
Maintains endometrium and pregnancy.
Thicken cervical mucus.
Inhibits further secretion of GRH, FSH and LH, this prevents further follicles developing.

20
Q

Important pharmacological TARGETS in the regulation of ovulation and pregnancy

A

GnRH, FSH, LH all require to induce follicle formation and ovulation.
ER and PR agonist
Oestrogen and progesterone is required to feedback on hypothalamus and pituitary and so inhibit further follicles being formed.
ER and PR agonist
Progesterone is required to maintain pregnancy.
PR antagonist

21
Q

Combination pill (ER and PR agonist)

A

Oestrogen inhibits secretion of FSH via negative feedback.
This prevents development of ovarian follicle and blocks ovulation by blocking the FSH peak.
Progesterone inhibits secretion of LH, (negative feedback) prevents ovulation by blocking the LH surge and also makes the cervical mucus less suitable for passage of sperm.
Taken for 21 days then a 7 day pill free period causes withdrawal bleeding (false period)

22
Q

Progesterone only pill (PR agonist)

A

Mainly works by inhibiting LH - thickening the mucus in the cervix to stop sperm reaching the egg.
Progesterone only pill can also block ovulation (blocking the LH surge) although not consistently as FSH peak can still occur.
Taken continuously, can cause irregular periods.

23
Q

Emergency contraception - PR antagonist

A

Contragestation (abortion pill)
Mifepristone (RU 486)
Progesterone antagonist
Terminates pregnancy at the level of endometrium
Progesterone is responsible for maintaining pregnancy.

24
Q

Clinical targeting of female sex hormones

A

Oral contraceptives/fertility control - ER and PR agonist.
Replacement therapy in menopause - ER and PR agonist.
Ovulation induction - Mainly FSH and LH, also partial ER agonist - clomiphene citrate.
Cancer chemotherapy - ER antagonists or SERMs

25
Q

Hormone antagonists

A

Breast cancer - SERM (Selective oestrogen receptor modulator)
Prostate cancer - Androgen receptor (AR). Signal transduction plays an important role in prostate cancer.

26
Q

Mechanism of tumour action

A

Tumours arising in hormone sensitive tissue such as breast, endometrial, ovarian (oestrogen/progesterone receptors), prostate (androgen receptor) may be hormone dependent.

27
Q

Tumour growth may be inhibited by…

A

Oestrogen/progesterone/androgen receptor antagonists.

Agents that inhibit the synthesis of the oestrogen, progesterone and testosterone.

28
Q

ER and breast cancer treatments

A

Tamoxifen - SERM
Anastrozole - Aromatase inhibitor
Used in breast cancer treatment and preventation
75% of breast cancer are oestrogen receptor (ER) positive.

29
Q

Tamoxifen

A

A competitive inhibitor of estradiol binding to the oestrogen receptor (ER).
Tamoxifen binds to the ER to form a dimer.
Tamoxifen:ER dimer.
Then transported from the cytosol to the nucleus where it binds to DNA to form an unstable complex.
Hormonal growth signal is switched off = Reduced cell proliferation.

30
Q

Anastrozole

A

Hormonal growth and survival signal is switched off = reduced cell proliferation and cell survival

Pharmacology PED1003 (18 decks)

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