Reproductive System Week 2 Flashcards
What is required for successful reproduction?
Each sex to produce right number of gametes at right time
Effective apparatus to transfer sperm from male to female
The creation of opportunities to use that apparatus
Sperm transport and fertilisation
Support of the conceptus, embryo and foetus
Successful parturition
Support of the neonate
Where are the major controlling structures of reproduction located in males and females?
The hypothalamus, pituitary gland (particularly anterior), gonads, and placenta (in pregnant females)
How do the controlling structures of reproduction interact with each other?
Primarily by secretion of hormones
Where does the anterior pituitary gland arise from embryologically?
Rathke’s pouch
Hormones of which axis are crucial to reproduction?
Hypothalamic-pituitary-gonadal (HPG) axis
Which other glands are regulated by the hypothalamus-pituitary unit?
Thyroid (HPT)
Adrenal (HPA)
What other actions does the hypothalamus-pituitary unit control?
Somatic growth, lactation, milk secretion, water metabolism
Where does the pituitary gland sit?
In the sella turcica of the sphenoid bone of the skull
Beneath the hypothalamus
What is the alternative name for the anterior pituitary gland?
Adenohypophysis
What is the alternative name for the posterior pituitary gland?
Neurohypophysis
What is the embryological origin of the pituitary gland?
Ectoderm
What tissue makes up the posterior pituitary gland?
Nervous tissue
How is the posterior pituitary gland connected to the hypothalamus?
Physical connection
Hypothalamus drops down through the infundibulum to form the posterior pituitary gland
How does the anterior pituitary gland communicate with the hypothalamus?
The hypophyseal portal system
Superior hypophyseal artery
Where in the hypothalamus is oxytocin released from?
Supraoptic nucleus
Where in the hypothalamus is ADH released from?
The Paraventricular nucleus
Describe the function of the posterior pituitary gland
Oxytocin and ADH produced by neurones in hypothalamus
Transported down nerve cell axons to posterior pituitary
Stored and released from posterior pituitary into circulation to act on distant targets
Describe the function of the anterior pituitary gland
Hormones produced in the hypothalamus are transported down axons and stored in the median eminence before being released into the hypophyseal portal system
These hormones act on target endocrine cells in the anterior pituitary
Endocrine cells of the anterior pituitary secrete hormones into the blood stream to act on distant target cells
What function do the hormones released by the hypothalamus have?
Neurocrine function
Both direct effects on distant tissues (from posterior pituitary) and tropic effects on endocrine cells of anterior pituitary
What function do the hormones released by the anterior pituitary gland have?
Endocrine, autocrine and paracrine functions
Describe the hormones produced by the hypothalamus and their function
Oxytocin - milk let down, uterine contractions
ADH - water regulation
Tropic:
TRH - thyrotropin releasing hormone - stimulates release of TSH and prolactin
PRH - prolactin releasing hormone - stimulates release of prolactin
PIH - prolactin release-inhibiting hormone - inhibits release of prolactin
CRH - corticotropin releasing hormone - stimulates release of ACTH
GnRH - Gonadotropin releasing hormone - stimulates release of LH and FSH
GHRH - growth hormone releasing hormone - stimulates release of growth hormone
GHIH (Somatostatin) - growth hormone inhibiting hormone - inhibits release of growth hormone
Describe the hormones produced by the anterior pituitary gland and their function
TSH - stimulates thyroid hormone release from thyroid gland
ACTH - stimulates secretion of hormones from adrenal cortex
LH - ovulation and secretion of sex hormones
FSH - development of eggs and sperm
PRL - mammary gland development and milk secretion
GH - growth and energy metabolism - stimulates IGFs
How is the hypothalamus pituitary unit regulated?
Negative feedback
Describe the characteristics of hormones released by the hypothalamus
Secretion in pulses tied to internal biological clock (synchronised external signals e.g. Light)
Act on specific membrane receptors
Transduce signals via second messengers
Stimulate release of stored pituitary hormones
Stimulate synthesis of pituitary hormones
Stimulates hyperplasia and hypertrophy of target cells
Regulates own receptor
What does the HPG regulate
Development
Reproduction
Ageing etc.
Describe GnRH and its release
10 AA peptide
Release is pulsatile (every 1-3 hours, lasting 5-25 minutes)
Intensity of stimulus affected by frequency of release and intensity of release
Which cells does GnRH act on?
Gonadotrophs of the anterior pituitary gland
What percentage of the anterior pituitary gland is made up by gonadotropic cells?
5-10%
What happens in the absence of GnRH?
Gonadotropic cells produce little to no FSH or LH
Describe the control of GnRH secretion by the hypothalamus in the male
Influenced by other parts of brain (e.g. Body weight, Outside environment)
Testosterone reduces secretion of GnRH
Describe the control of GnRH secretion from the hypothalamus in the female
Influenced by other areas of brain (e.g. Body weight, outside environment)
Oestrogen (mainly oestradiol) at intermediate concentrations reduces secretion of GnRH - reduces amount produced per pulse
Progesterone increases inhibitory effect of oestrogen - through reducing the frequency of pulses
Oestrogen alone at high concentrations promotes the release of GnRH –> surge
Progesterone prevents a surge at high oestrogen levels
Describe the control of FSH and LH secretion from the anterior pituitary in both sexes
Amount of FSH and LH secreted in each pulse is affected by oestrogen at intermediate concentration (reduces it)
Oestrogen at high concentration (increases it)
Amount of FSH produced in response to GnRH is reduced by inhibin
Testosterone will reduce the sensitivity of gonadotrophs to GnRH (-) FSH and LH
Describe the control of hormonal secretion by the ovary in the antral phase
LH binds to theca interna cells – > stimulate them to produce androgens (androstenedione)
FSH binds to granulosa cells –> stimulates them to develop enzymes which convert androgens to oestrogens
As follicle grows more oestrogens produced for a given gonadotropic stimulation
Describe the control of hormone secretion by the ovary in the pre-ovulatory phase
LH receptors develop in outer layers of granulosa cells
Lots of oestrogen produced
Surge of LH stimulates ovulation
Describe the control of hormone secretion by the ovary in the post-ovulation phase
LH stimulates the corpus luteum to secrete progesterone and oestrogen
As the corpus luteum grows more steroids are produced for a given LH concentration
Inhibin released from granulosa cells of corpus luteum –> inhibits secretion of FSH from anterior pituitary (same as males) and has small inhibitory effect on LH
What is the major difference between the control of hormone secretion from the gonads in females and males?
The amount of testosterone secreted for a given LH concentration is relatively constant where as the events of the ovarian cycle influence the response to gonadotropins producing an ovarian or pelvic clock
What is the name for the variation in response to gonadotropins over the ovarian cycle?
The ovarian or pelvic clock
Describe the control of hormone secretion from the testes
LH acts on Leydig cells –> promotes testosterone secretion (enhanced by prolactin and inhibin)
Testosterone diffuses into seminiferous tubules
FSH acts on Sertoli cells –> makes them grow and secrete spermatogenic substances and become responsive to testosterone
Testosterone acts on Sertoli cells to promote spermatogenesis
Testosterone acts elsewhere in the body to maintain male reproductive system (Determinative and regulatory effects)
Testosterone inhibits GnRH secretion from hypothalamus and reduces sensitivity of gonadotrophs to GnRH
If spermatogenesis proceeds too rapidly - inhibin secreted from Sertoli cells - reduces secretion of FSH from gonadotrophs
Describe the actions of FSH and LH in the male (briefly)
Act via GaS
PCR –> adenylate cyclase
Stimulate sex hormone synthesis (steroidgenesis)
Control gamete production (spermatogenesis)
How much testosterone is typically produced per day in the male ?
4-10 mg per day
Relatively constant in medium-long term
Circadian rhythm (highest in morning)
Environmental stimuli have an effect
Describe the actions of FSH and LH in the female (briefly)
Acts on GaS
PCR –> adenylate cyclase
Stimulates sex hormone synthesis (steroidgenesis)
Controls gamete production (folliculogenesis and ovulation)
What is an alternative name for the pituitary gland?
Hypophysis
What class of hormones do testosterone, progesterone and oestrogen belong to?
Steroid hormones
What is the function of androgen binding protein?
Produced by the Sertoli cells
Binds specifically to testosterone
Makes it less lipophilic –> concentrates it in the seminiferous tubules
The high levels of testosterone enables spermatogenesis and sperm maturation
What happens to the HPG axis in males with age?
FSH and LH start to rise at age 20 and testosterone slowly declines after age 40
What is different about the release of FSH v.s. LH?
LH release is pulsatile where as FSH release is not
FSH release depends on the intensity of GnRH release
What are pars distalis and pars nervosa?
The anterior and posterior pituitary gland
What are the two phases of the menstrual cycle?
Follicular or proliferative phase
Luteal or secretary phase
What happens in the follicular phase? (Briefly)
The ovaries and reproductive tract etc. Are prepared for ovulation
To maximise the chance of fertilisation
What happens in the luteal phase? (Briefly)
Wait for signal from the developing placenta
Physiological changes occur in preparation for potential pregnancy
If no signal - cycle ends and new one begins
When does the menstrual cycle begin?
First day of menstruation (though this is physiologically the end of the previous cycle)
How long is the follicular phase?
12-14 days
Variable
How long is the luteal phase?
14 days
How long is the menstrual cycle?
21-35 days
Varies among different women and in the same woman
When does ovulation occur?
Usually day 14 of the menstrual cycle
Describe the levels of gonadotropins and steroid hormones in the follicular phase
The early follicular phase: - low levels of oestrogen and inhibin lead to... - Relatively high levels of FSH and LH - Low but rising levels of oestrogen - Very low levels of progesterone Late follicular phase: - FSH levels fall due to inhibin secretion - LH levels rise - Oestrogen levels rise dramatically - Leading to surge in LH levels - Ovulation occurs
Describe the levels of gonadotropins and steroid hormones in the luteal phase
Early:
- FSH and LH are low due to decrease in oestrogen
- Low levels of progesterone, increasing
Late:
- FSH and LH continue to decrease
- Progesterone and oestrogen increase to high levels (progesterone higher than oestrogen)
- Progesterone falls and then oestrogen falls
- Menstruation begins
Which gonadotropin causes ovulation?
LH
Which gonadotropins maintain the corpus luteum?
FSH and LH
What is the ovarian cycle?
Preparation of the gamete for ovulation and fertilisation
What is the uterine cycle?
Preparation of the endometrium for ovulation and fertilisation
How long after ovulation can a signal be produced indicating that fertilisation has occurred?
14 days
Where do gonadotropins act?
On the ovary
Where do steroid hormones / ovarian steroids act?
Act on tissues of the reproductive tract
Control the cycle
What class of hormones does inhibin belong to?
Peptide hormone
Describe the actions of gonadal steroids in the follicular phase
Stimulate secretion and muscular contraction of the Fallopian tube and the growth and motility of fallopian cilia
Stimulate growth and motility of myometrium
Stimulate thickening of the endometrium and increase in number and size of glandular invaginations - cells secrete watery fluid conductive to sperm
Stimulate secretion of cervical mucous which is thin and alkaline - conductive to sperm transport
Stimulates increased mitotic activity in vaginal epithelium
Stimulates mildly anabolic metabolic changes, depresses appetite and maintains bone structure
Has effects on the CVS
Hair, skin changes
What is the consequence of progesterone stimulation of oestrogen primed cells in the luteal phase?
Reduces Fallopian tube motility, secretion and cilia motility
Stimulates further growth of myometrium but reduces motility
Stimulates further thickening of the endometrium, increased secretion and development of the spiral arteries
Stimulates thickening and acidification of cervical mucous - inhibits sperm transport
Stimulates a mildly catabolic metabolic change
Elevates basal body temperature
Promotes change in salt and water excretion which may in combination with high oestrogen produce net sodium and water retention
Changes mammary tissue
What is the effect on the uterine cycle of a sudden fall in progesterone and oestrogen?
The secretary epithelium of the endometrium undergoes apoptosis
Tissue is shed as a menstrual bleed
The spiral arteries contract to reduce blood loss
Describe the follicular phase of the menstrual cycle
Day 0 - oestrogen, progesterone and inhibin levels low
GnRH secretion released from inhibition
LH and FSH rise
FSH rises more due to additional effect of reduced selective inhibition at the pituitary by inhibin
FSH, followed by LH, cause follicles to grow
Oestrogen and inhibin secretion rises
FSH secretion selectively inhibited by inhibin
LH receptors develop on granulosa cells
As the follicles grow more and more oestrogen is released for the same amount of LH concentration
Rising levels of oestrogen causes positive feedback on GnRH
Leads to LH surge - precise timing of this may be influenced by environmental factors
LH surge produces ovulation
Describe the luteal phase of the menstrual cycle
Because the ovum has been released, oestrogen levels drop dramatically
The corpus luteum forms spontaneously
LH promotes secretion of oestrogen and progesterone from corpus luteum
Rising oestrogen levels do not exert positive feedback on GnRH due to progesterone levels rising
Exert a negative feedback - causing LH FSH and GnRH to fall
In absence of pregnancy corpus luteum regresses spontaneously 14 days after ovulation
Therefore progesterone and oestrogen levels fall
This triggers a menstrual bleed
Relieving inhibition of FSH and LH –> triggers development of new follicles and beginning of new cycle
What happens if conception has occurred?
The implanted embryo develops a placenta which secretes human chorionic gonadotropin
This prevents regression of corpus luteum –> continues to secrete oestrogen and progesterone until placenta takes over
Supports the early weeks of pregnancy
Maintains suppression of the ovarian cycle
Describe the effect of menopause on gonadotropins and gonadal steroids
No developing follicles
Oestrogen decreases
Therefore GnRH, FSH and LH increase
FSH increases more than LH due to reduced inhibin secretion as well as reduced oestrogen
What is clomephine and how does it work?
It is an “anti-oestrogen” used in the treatment of infertility
Exerts weak oestrogenic effect - achieves binding and uptake by oestrogen receptors
Reduces the concentration of oestrogen receptors by inhibiting receptor replenishment
Therefore the hypothalamic-pituitary axis is blinded to endogenous oestrogen levels
Given for 5 days at start of menstrual cycle
Reduces the inhibition of GnRH secretion caused by moderate levels of oestrogen
Therefore GnRH secretion increases, increasing FSH and LH levels
What is bromocriptine and how does it work?
An analogue of dopamine (PIH)
Works by inhibiting prolactin secretion which restores the pulsatile secretion of GnRH to normal and therefore increases fertility
What are haloperidol, metoclopramide and domperidone and how do they work?
Dopamine antagonists
Increase prolactin secretion
Prolactin acts to disturb the pulsatile release of GnRH, decreasing fertility
What is HCG analogous to?
LH
Acts on the corpus luteum to increase progesterone and estranged secretion
What factors can affect the menstrual cycle?
Low body weight
Emotional stress
Pregnancy
Lactation
