4.1 Hormonal control of reproduction Flashcards
What is the HPG axis
hypothalamus -> anterior pituitary -> gonads
Compare the anterior and posterior pituitary, give 3 hormones released from each
Anterior pituitary: GH, FSH, LH
- Arises from Rathke’s Pouch
- Not nervous tissue
- Endocrine gland
- Mostly ‘trophic’ hormones
Posterior pituitary: Oxytocin, ADH
- Nervous tissue
- Neurosecretory gland
What is Oxytocin important in?
Hormone release from the PP that is important in reproduction:
- Social interaction
- Orgasm
- Labour
- Lactation
List 3 types of glycoprotein hormones and what cell type secretes them
LH, FSH secreted by gonadotrophs
TSH secreted by thyrotrophs
List 3 types of polypeptide hormones and what cell type secretes them
GH secreted by somatotrophs
ACTH secreted by corticotrophs
Prolactin secreted by lactotrophs
Anterior pituitary secretions are controlled by the hypothalamus via releasing hormones, how do these travel?
Travel in hypophyseal portal circulation
What is a key releasing hormone of reproduction?
How often is this released?
Gonadotrophin releasing hormone (GnRH)
Release is pulsatile (about once an hour)
What do pulsatile secretions of GnRH do?
stimulates gonadatrophs in anterior pituitary to secrete FSH & LH
FSH and LH act on the gonads, what 2 things does this do?
1) Control gamete production
2) Stimulate secretion of gonadal steroids
What do the gonadal steroids act on?
List what these are in both males and females
Released from the gonads and act on the reproductive tract
Males: testosterone
Females: oestradiol and progesterone
How do we control the release of GnRH from neurones? (3)
1) Influenced by other neurones ➞ KISS 1 neurone
2) Environmental effects eg. body weight (Influence KISS1 or GnRH directly)
3) Feedback from gonadal hormones/sex steroids
What is the effect of testosterone on GnRH?
What is the effect of testosterone on FSH and LH
Reduces in both
What are the effects of moderate titres of oestrogen on GnRH and therefore FSH and LH? What type of feedback is this?
What are the effects of moderate titres of oestrogen on GnRH and therefore FSH and LH? What type of feedback is this?
Moderate titres of oestrogen reduce GnRH, FSH and LH secretion
• Negative feedback
High titres of oestrogen promote GnRH, FSH and LH secretion
• Positive feedback
• LH ‘surge’
What is the effect of progesterone on oestrogen in females? (explain the effects at moderate and high oestrogen levels)
Progesterone increases inhibitory effects of moderate oestrogen
Progesterone prevents positive feedback of high oestrogen ➞ No LH surge
How do oestrogen and progesterone affect GnRH amount and frequency
Oestrogen reduces GnRH per pulse (amount)
Progesterone influences frequency of pulses
What do amount and proportion of LH and FSH depend on?
Additional signalling molecules acting on gonadotrophs eg. Gonadal steroids, inhibin, activins
(LH and FSH are controlled independently)
Explain the role of Inhibin and state what cells produce this in both males and females
The amount of FSH and LH secreted in response to GnRH is reduced by inhibin (Inhibin works MORE on FSH than LH)
Secreted by granulosa cells (f) and Sertoli cells (m)
Explain the role of Activins
What produces these?
Activins have many local actions but also feedback to the pituitary to activate FSH secretion
Activins are secreted by the gonads and other tissues
Explain the role of FSH, what cells do these bind to in males?
FSH binds to Sertoli cells to stimulates spermatogenesis
Explain the role of LH, what cells do these bind to in males?
What are the 3 things does this result in (in terms of spermatogenesis)
LH binds to Leydig cells to secrete testosterone (promotes spermatogenesis) resulting in:
1) Spermatogonial mitotic steps
2) Sertoli cell interactions with gametes
3) Sperm release
What 2 hormones can enhance testosterone production?
Enhanced by prolactin and inhibin (but these cannot replace LH)
What is the role of Testosterone on the HPG axis?
How does this ensure we have the correct levels of testosterone?
Testosterone is secreted by Leydig cells in response to LH binding and acts on the reproductive tract
Testosterone negatively feeds back to the Hypothalamus to decrease GnRH secretion
Hence if testosterone levels get high, GnRH and therefore LH levels fall bringing testosterone levels back to normal range
How can we measure rate of spermatogenesis in males?
How does this ensure we achieve the correct rate of spermatogenesis?
Inhibin secretion is a marker of the rate of spermatogenesis in males
If spermatogenesis speeds up MORE inhibin is secreted which reduces FSH secretion bringing rates back to normal
What are the actions of Testosterone on the male reproductive tract?
1) Stimulates gamete production
2) Maintains epididymis and vas deferens
3) Maintains prostate, seminal vesicles, bulbo-urethral glands
4) Production of semen
5) Development and maintenance of external genitalia and secondary sexual characteristics
6) Sexual dimorphism throughout the body and behaviour
Give 3 environmental factors that affect testosterone production
1) Circadian rhythm (testosterone highest early morning)
2) stress hormones
3) Neuronal inputs
What is the preparation phase in the female menstrual cycles also known as?
What 3 things occur during this phase?
‘Follicular’ or ‘proliferative’ phase
1) Follicles grow in ovary
2) Uterus prepared for sperm transport and implantation of conceptus
3) Changes to facilitate sexual interactions
Describe 3 changes in development AND hormones that occur during the beginning of the follicular phase
Development
1) Corpus luteum absent
2) Follicles only part developed
3) Little inhibition at hypothalamus or pituitary
Hormonal:
1) follicles secrete very little inhibin
2) Oestrogen and progesterone levels low
3) FSH levels rise
Describe 4 hormonal changes that occur during the middle of the follicular phase
Explain what these changes lead to?
Hormonal:
1) Oestrogen levels rising
2) Inhibin levels rising
3) LH levels rise (due to oestrogen)
4) FSH rising but less so (due to inhibin)
Leads to: Selective inhibition of FSH so NO new follicles can develop + Oestrogen exerts positive feedback at hypothalamus and pituitary (higher concentrations secreted by later stage follicles)
What hormonal change occurs during the pre-ovulatory phase and why?
Rising oestrogen levels create a window of opportunity for the LH surge and ovulation
Precise timing within it that is dependent on environment E.g. stress, copulation, circadian rhythms
What specific hormone changes are responsible for “ovulation” and why?
What 2 things occur immediately after ovulation?
Rise in oestrogen followed by LH surge causes ovulation. This allows a brief period of fertility
After ovulation:
1) Corpus luteum forms spontaneously and begins to secrete progesterone and oestrogen (maintains suppression of FSH)
2) LH is suppressed b/c positive feedback by oestrogen is now inhibited by progesterone
What is the waiting phase also known as?
What happens to the corpus luteum during this phase and why?
‘Luteal’ or ‘secretory’ phase
Corpus luteum grows and secretes more oestrogen (granulosa luteal cells) and Progesterone (thecal luteal cells). This facilitates placenta formation in endometrium
What stimulates the start of a new cycle?
After 7-10 days the corpus luteum starts to decrease in size and at day 14 undergoes autophagy. This stops the production of gonadal steroids ➞ stimulates menstruation
When this occurs there is no more inhibition on FSH secretion so FSH levels begins rising and a new cycle begins
What hormone changes specifically are responsible for “menstruation”
Progesterone and oestrogen titres fall
Explain the role of FSH and LH in each phase (3)
What cells do these bind to in females?
Follicular phase:
- FSH binds to granulosa cells
- LH binds to Thecal cells (theca interna)
Together these stimulate development of the follicle
Pre-ovulation:
- LH surge stimulates ovulation
Luteal phase: LH maintains corpus luteum
What is the dominant gonadal steroid during the follicular phase?
What does this stimulate?
oestrogen
1) Fallopian tube function
2) Thickening of endometrium
3) Growth & motility of myometrium
4) Thin alkaline cervical mucus
5) Vaginal changes
6) Changes in skin, hair, metabolism
7) Calcium metabolism
What is the dominant gonadal steroid during the luteal phase?
What does this stimulate?
Progesterone (acts on oestrogen primed cells)
1) Further thickening of endometrium into secretory form
2) Thickening of myometrium, but reduction of motility
3) Thick, acidic cervical mucus
4) Changes in mammary tissue
5) Increased body temperature
6) Metabolic changes
7) Electrolyte changes
Describe the histological gland changes seen during:
1) Early proliferative phase
2) Late proliferative phase
3) Early secretory phase
4) Late secretory phase
1) Early proliferative: glands sparse, straight
2) Late proliferative: functionalis has doubled, glands now coiled
3) Early secretory: endometrium maximum thickness, very pronounced coiled glands
4) Late secretory: glands adopt characteristic “saw-tooth” appearance
Compare the feedback mechanisms of males vs females
Males: negative feedback ONLY
Females: negative AND positive feedback
Explain the effects of FSH in females
What cells does this bind to?
FSH binds to granulosa cells which causes:
1) granulosa cells to secrete Inhibin
2) continued follicular development
3) increase in granulosa cells and more FSH receptors
4) development of Theca interna (contains LH receptors)
Explain the effects of LH in females
What cells does this bind to?
Binds to Theca interna around the developing follicle and causes it to secrete oestrogen
List 2 things that can influence timing of the female cycle?
1) Stress
2) Ovarian follicle quality
What happens if conception occurs?
What hormones are secreted here?
The developing embryo and the placenta secrete:
1) Human Chorionic Gonadotrophin (HGC) which preserves the corpus luteum
2) CL continues secretion of progesterone and oestrogen which maintains the uterine lining for implantation until placenta forms and is able to take over
The cycle does NOT start again
