Hormones and reproduction: the female Flashcards
What increases when the endometrium is growing?
Oestrogen
What are oocytes and what causes reactivation?
Oocytes (eggs) are stored in fetal life and are inactive. Menarche (puberty) happens around 12 years old and causes the reactivation of oocytes
What phases follow menstruation in the menstrual cycle?
Follicular phase (days 5-14) - can be variable in length, then luteal phase (ovulation) (days 14-28)
What phases occur in the endometrium?
proliferative phase: when oestrogen stimulates regrowth of endometrium
Secretory phase: glands in the endometrium are secretory
What does progesterone support?
pregnancy - PROgesterone
What does the peak of progesterone coincide with and when does this peak occur?
Coincides with Oestrogen about a week after ovulation
What are oestrogen and progesterone?
Steroid hormones - fat soluble chemicals
Where does the surge of LH and FSH occur?
Just before day 14 (ovulation)
What are LH and FSH?
Gonadotropins - polypeptide hormones (water soluble). They regulate steroid production
What are the 4 female sex steroids and what do they have in common?
17beta-oestradiol (oestrogen) 17beta-oestrone 17beta-oestriol Progesterone - they all contain 4 fused carbon rings, and oestrogens are unusual in that they have an aromatic ring unlike any other steroids
What gives rise to oestrogen compounds?
Androgens:
androstenedione –> Estrone
testosterone –> 17beta-estradiol
What catalyses the conversion of androgens to oestrogen compounds?
Aromatase enzyme
What is the most potent oestrogen compound?
17beta-estradiol (E2)
What is the precursor of all steroid hormones?
cholesterol
What do circulating hormones require?
Receptors in target tissues. The major steroid receptors are INTRACELLULAR - in the cell nucleus
What family do receptors for all the major classes of steroid hormome (androgens, oestrogens, progestins etc) belong to?
Nuclear receptor superfamily
How many binding sites do the receptors have?
2 - one for steroid and the other for DNA
What does binding of the steroidal ligand do?
Produces a complex that acts on DNA - conformational change in receptor when streroid binds
What does the binding of the complex onto DNA do?
Alters the repertoire of genes being expressed by target cells. This activity defines the steroid receptors as transcription factors
Why do gonadotropins need receptors at the cell surface?
(FSH, LH) - need receptors at cell surface because they are water soluble and cannot pass cell membrane
How is the production of the gonadotropins regulated?
HPO axis: hypothalamus releases GnRH which travels to anterior pituitary, production from hypothalamus is pulsatile. As hormone concentration rises, receptors get saturated (max turnover). The action of GnRH is to stimulate the release of gonadotropins and they travel through the blood to the ovary which produces sex steroids and a dominant follicle which will ovulate to produce an egg
What does the stimulatory action of GnRH at the anterior pituitary depend on?
Pulse frequency NOT amplitude
What do the gonadotropins control?
sex steroid production and follicle maturation/ovulation
What is GnRH?
Gonadotropin releasing hormone (GnRH).
10 amino acids
Acts as the GnRH receptor (a G protein coupled receptor (GPCR))
Stimulates the release of FSH and LH
How can GnRH be affected by sex steroids?
downstream of GnRH - sex steroids can feedback
How many pulse frequencies does the anterior pituitary gland give?
2:
- fast pulse frequencies = LH
- slow frequencies = FSH
What causes the LH peak surge right before ovulation?
GnRH pulsatility frequency increases resulting in a surge of LH (fast frequencies)
How is GnRH used in assisted reproduction?
GnRH agonists and antagonists are both used used to shut down the ovary in advance of a controlled cycle to collect eggs
What is Buserelin?
An agonist at the GnRH receptor It can stimulate FSH and LH production but long term constant levels cause: - GnRHR down-regulation - resulting insensitivity to GnRH - loss of production of FSH and LH
What controls the onset of puberty?
Leptin - which is released by fatty tissues, - affects GnRH hence why puberty can occur earlier in girls overweight
What is early puberty associated with?
Type 2 diabetes and cardiovascular disease in women and men
What is increasing age at menarche associated with?
Higher risks for osteoporosis but lower risks for breast cancer
What produces progesterone and oestrogen?
Corpus luteum
What stimulates ovulation?
LH
What happens to the number of follicles in the follicular phase of the ovarian cycle?
There is a cohort of follicles recruited each month of 20 and eventually 19 die off for 1 to become the dominant follicle.
What does the follicle enlarger under the presence of?
Oestrogen
What is released during ovulation?
Oocytes, alongside some somatic cells (granulosa cells) and also the liquid inside a follicle
How many phases are there of meiosis?
TWO - take place in the ovary (only 1 phase in mitosis)
In the female, what is positive feedback by steroid to the hypothalamus?
negative feedback
Describe what happens to the levels of FSH and Oestrogen in the follicular phase
Production of oestrogen at low levels.
FSH starts to rise to promote the development of cohort of follicles
FSH then starts to decline which coincides with the increase of oestrogen.
Oestrogen increase causes a negative feedback on hypothalamic production of GnRH which then stops FSH frim increasing as enough follicles have been produced.
Positive feedback of oestrogen then occurs that gives the spike of LH just before ovulation
What feedback occurs in the late luteal phase?
2 negative feedbacks from oestrogen and progesterone
Post ovulation, what happens to the levels of LH and FSH?
levels decline
How many hours before ovulation does the LH spike occur?
36 hours
What feedback occurs in males?
Androgen feeds back negatively - there is no positive feedback
What inhibits GnRH?
Combind E2 (estradiol) and P (progestin). Prolonged high E2 alone also has this effect (more side effects - endometrial cancer)
What happens to the lumen as the endometrium grows?
Contracts
Where does a steroid bind and what effects does this have on mRNA?
Steroids bind to their receptors - the complex then goes to the nucleus of DNA and binds to a subset of genes that contain a specific sequence called a response element (SRE). This stimulates the increase in rate of mRNA transcription. Allows gene to respond in the presence of a steroid
What is faslodex?
A pure anti-oestrogen that binds to the oestrogen receptor and blocks its ability to activate target genes and therefore cannot increase mRNA transcription
What is tamoxifen?
Long standing anti-breast cancer drug - partial antagonist/ partial agonist
What is menopause?
permanent cessation of ovarian activity usually said to have occurred after 12 consecutive months of amenorrhoea
What is perimenopause?
period before menopause and 1st year after it
What is climacteric?
transition from reproductive life to non-reproductive state
What are vasomotor symptoms?
Associated with menopause, attributed to fluctuations in oestrogen levels.
Low dose oestrogen therapy is sufficient to counter flushes
What dose oestrogen is required to stimulate receptors in the vagina to lower urethra?
around 10microg a day
What effect does eostrogen have on cognitive function?
Can improve some aspects of cognitive function and improve depression scores
What happens to wound healing after menopause?
It’s slower
What is the relationship between bone density and oestrogen?
Bone density decreases with declining oestrogen
What sort of agent is oestrogen?
Anti-inflammatory agent
