Session 2: Control of Reproductive Processes Flashcards
What does successful reproduction require?
[*] Each sex to produce the right number of gametes at the right time
[*] An effective apparatus to transfer sperm from male to female
[*] The creation of opportunities to use that apparatus
[*] Effective sperm transport and fertilisation
[*] Support of the conceptus, embryo and fetus
[*] Successful parturition
[*] Support of the neonate
[*] Hormones are involved in the control of all of these processes.
Describe the importance of the Hypothalamic-Pituitary-Gonadal Axis
[*] In both male and female, the major controlling structures are located in the hypothalamus, the pituitary gland (particularly the anterior pituitary) and the gonads.
[*] In the pregnant female, important control is also exerted by the placenta.
Describe the importance of the pituitary gland
[*] The posterior pituitary is nervous tissue (grows down from the brain) and is a neurosecretory gland (hormones are released from the axons of neurones in the brain, which run down to the posterior pituitary). It secretes ADH and Oxytocin. Oxytocin is important in reproduction (particularly in the latter stages around birth).
[*] Anterior pituitary is not nervous tissues – arises embryologically from Rathke’s Pouch. It is an endocrine gland (hormones secreted directly into the bloodstream).
[*] Each secretory cell type in the anterior pituitary is controlled by releasing (and sometimes inhibitory) hormones, produced by nerve cells in the hypothalamus, which pass to the anterior pituitary in the hypophyseal portal vessels.
This specialised portal circulation allows a small volume of arterial blood to carry small concentrations of hormones in concentrated form to the anterior pituitary – the releasing hormones are not diluted by the systemic circulation (much larger volume).
Releasing hormones are neurosecreted directly from median eminence to anterior pituitary.
Dopamine has inhibitory effect on the release of prolactin from the anterior pituitary.
[*] Many pituitary hormones are trophic hormones, which act on other endocrine tissues to promote the secretion of further hormones.
The main reproductive anterior pituitary hormones, FSH and LH, are produced by gonadotrophs, controlled by one releasing hormone: Gonadotrophin Releasing Hormone (GnRH)
List which cell types in the anterior pituitary gland produce which hormones
NB: Gonadotrophs secrete gonadotrophins in response to the pulses of GnRH. In the absence of GnRH, no LH or FSH is secreted.
Describe what influences the secretion of GnRH from the hypothalamus
Several groups of hypothalamic neurones secrete Gonadotrophin Releasing Hormone (GnRH) under the influence both of other structures in the brain (and hence the environment via sensory input) and circulating hormones.
- All secrete GnRH in a pulsatile fashion – a burst of secretion about once an hour. NOT CONTINOUS.
- Pulsatile secretion stimulates gonadatrophs to secrete FSH and LH.
[*] Amount of LH and FSH secreted depends on other factors acting on gonadotrophs.
[*] Proportion of FSH and LH influenced by other factors acting on gonadotrophs.
Gonadal steroids influence GnRH-secreting neurones in the hypothalamus (feedback from gonads). The neurones are also affected by their connection to other parts of the brain influenced by factors such as body weight and changes in the environment.
Describe the influence of testosterone on the secretion of GnRH, FSH and LH
- Testosterone reduces secretion of GnRH (negative feedback)
- In the anterior pituitary, testosterone reduces LH and FSH secretion.
Describe the influence of oestrogen and progesterone on the secretion of GnRH, LH and FSH
- Oestrogen (principally oestradiol) at intermediate concentration reduces secretion of GnRH (negative feedback)
- Progesterone increases the inhibitory effect of oestrogen
Moderate oestrogen reduces the amount of GnRH secreted per pulse, progesterone reduces the frequency of pulses
- Oestrogen alone at high concentration promotes the release of GnRH, producing a ‘surge’ of LH – which is a timing signal (triggers ovulation). POSITIVE FEEDBACK.
Progesterone prevents high levels of oestrogen producing a GnRH surge (so no LH surge). Progesterone is never present on its own – always present with oestrogen.
In the anterior pituitary, the amount of FSH and LH secreted in response to each pulse of GnRH is affected by
[*] Oestrogen at intermediate concentration which reduces FSH and LH secretion
[*] Oestrogen at high concentration which promotes FSH and LH secretion
Describe the action of Inhibin. Where is it produced?
The amount of FSH secreted in response to GnRH is reduced by inhibin – a protein hormone produced by developing ovarian follicles (granulosa cells) and in seminiferous tubules (Sertoli cells)
[*] Inhibin has virtually no effect on LH.
- Inhibin secretion is proportional to developing gametes – the more developed the gametes, the more Inhibin secreted.
Describe the primary actions of gonadotrophins
FSH and LH act primarily on the gonads to influence the production of gametes and to promote the secretion of gonadal steroids.
[*] Oestradiol and progesterone in the female
[*] Testosterone in the male
[*] In the absence of LH and FSH, no gonadal steroids are secreted.
Steroids control other reproductive processes but also act as signals to the control system itself.
Describe the action of LH and FSH on testosterone secretion and spermatogenesis
Male: in the testis, LH stimulates the secretion of testosterone by Leydig (interstitial) cells.
[*] Men secrete 4-10mg each day.
[*] The amount of testosterone secreted at a given LH level is relatively constant.
[*] LH acts upon Leydig cells to promote the secretion of testosterone, promotes spermatogenesis. The effects of LH are enhanced by prolactin and inhibin.
[*] Testosterone acts on Sertoli cells to promote spermatogenesis.
[*] FSH binds to Sertoli cells. Spermatocytes can only pass into the spermatic tubules via FSH-stimulated Sertioli cells; FSH maintains Sertoli cells and makes them responsive to testosterone so FSH first, LH later
[*] Testosterone acts elsewhere in the body to maintain the male reproductive system.
[*] FSH maintains Sertoli cells and makes them responsive to testosterone
- So long as LH and FSH are appropriate, both spermatogenesis and testosterone secretion (and hence the rest of the reproductive system) will be maintained.
Describe how levels of testosterone and rate of spermatogenesis are kept constant and the importance of this
The male must produce sperm constantly and be ever ready to deliver them to the female. This requires constant, appropriate levels of FSH, LH and testosterone which are achieved by negative feedback:
[*] If testosterone levels tend to rise, this will inhibit GnRH secretion, so reducing production of LH and FSH
[*] Levels are further reduced by testosterone reducing sensitivity of gonadotrophs to GnRH
[*] So testosterone levels fall back to normal range.
[*] If spermatogenesis proceeds too rapidly, inhibin levels rise (more Inhibin is secreted). Inhibin secretion by Sertoli cells is related to rate of spermateogenesis.
[*] Inhibin reduces secretion of FSH by acting on gonadotrophs in the pituitary (so Sertoli cells are less response to testosterone – decreases rate of spermatogenesis, bringing rate back to normal).
[*] Hormone levels therefore constant in medium and long term and there is a constant rate of production of sperm.
[*] 2 parallel negative feedback loops.
Is the level of testosterone always constant then?
In the medium and long term testosterone levels constant but it is variable over minutes and hours (constant over days).
[*] Circadian (daily) rhythm – highest early morning
[*] Effects of environmental stimuli
[*] Both driven by brain
Describe the role of hormones in the pre-antral phase of the female
- Cells of the theca interna bind LH.
- Granulosa cells bind FSH
- LH stimulates thecal cells to produce androgens (principally androstenedione). Theca interna develops.
- FSH stimulates granulosa cells to develop enzymes which convert these androgens to oestrogens. FSH also stimulates secretion of inhibin.
- This stimulates development of follicle. As the follicle grows, more oestrogens (stimulated by LH) are produced for a given gonadotrophic stimulation
- In the mid follicular phase, oestrogen levels are rising. Inhibin levels are rising leading to selective inhibition of FSH so no new follicles can develop. Oestrogen exerts positive feedback at hypothalamus and pituitary => LH levels rise but not FSH
Describe the role of hormones in the pre-ovulatory phase
- Follicle has grown a lot and is producing a high amount of oestrogen.
- LH receptors develop in outer layers of granulosa cells.
- High oestrogen positively feeds back. Rising oestrogen increases chance of LH surge.
- Precise timing may be influenced by environmental factors (clues from other species) however there is little evidence for circadian effects, some evidence of effects of copulation, lots of evidence for effects of stress (menstrual cycle gets delayed etc) so precise timing of ovulation is affected by environment.
- The window of opportunity: rising oestrogen levels create a window of opportunity for ovulation. Precise timing within it dependent on environment.
- A ‘surge’ of LH will stimulate ovulation (causes theca interna to weaken so follicle bursts)
- Follicle size increases, collagenase activity
- FSH is still being inhibited by Inhibin.
Describe the role of hormones post ovulation
- Remains of follicle reorganise themselves into the corpus luteum
- LH stimulates the corpus luteum to secrete progesterone and oestrogen.
- As the corpus luteum grows, more steroids are produced at a given LH concentration. More progesterone is secreted than oestrogen.
- Progesterone prevents positive feedback – acts via negative feedback and prevents new follicles from developing (maintains suppression of FSH).
- LH is also suppressed because positive feedback inhibited by progesterone.
[*] In the female therefore, the events of the ovarian cycle provide a ‘timing signal’ via the effects of steroids on the hypothalamus and pituitary. This variation produces a so-called ‘ovarian’ or ‘pelvic clock’, which is important in controlling the reproductive cycle of the female.
What are the changes that occur in the follicular phase?
[*] In the follicular phase steadily rising titres of oestrogen:
- Stimulate secretion and muscular contraction in the Fallopian tube, and the growth and motility of Fallopian cilia
- Stimulate growth and motility of the myometrium
- Stimulate thickening of the endometrium and increase in number and size of glandular invaginations. The cells secrete a watery fluid conducive to sperm
- Stimulates secretion of cervical mucus which is thin and alkaline and also conducive to sperm transport
- Stimulates increased mitotic activity in the vaginal epithelium
- Stimulate mildly anabolic metabolic changes, depress appetite and maintain bone structure.
- Have effects on the cardiovascular system
What are the changes that occur in the luteal phase?
[*] In the luteal phase, the action of progesterone on oestrogen-primed cells
- Reduces fallopian tube motility, secretion and cilia activity
- Stimulates further thickening of the myometrium but reduces myometrial motility
- Stimulates further thickening of the endometrium, increased secretion and in particular the development of spiral arteries.
- Stimulates thickening and acidification of cervical mucus, inhibiting sperm transport.
- Stimulate a mildly catabolic metabolic change.
- Elevates basal body temperature
- Promotes change in salt and water excretion which may, in combination with oestrogen lead to net sodium and water retention.
What happens after the luteal phase?
Sudden fall in oestrogen and progesterone
The elaborate secretory epithelium of the endometrium collapses – this is apoptotic cell death. The tissue is shed as a menstrual bleed, spiral arteries contract to reduce bleeding.
The uterine cycle is produced by steroids
Describe the hormonal characteristics of the phases of the menstrual cycle
The menstrual cycle is deemed to begin on the first day of menstrual bleeding, even though this is physiologically the end of the previous cycle. The cycle is coordinated by hormones: gonadotrophins and gonadal steroids (oestrogen, progesterone)
The follicular phase is variably 12-14 days long, the luteal phase 14 days.
[*] The early follicular phase is characterised by relatively high titres of FSH and LH, but rising titres of oestradiol and very low titres of progesterone.
[*] Later in the follicular phase, FSH levels fall, LH levels rise and oestrogen levels rise dramatically. Oestrogen peaks before ovulation.
[*] The rise in oestrogen is followed by the LH surge and ovulation
[*] In the early luteal phase, FSH and LH levels are low, with rising levels of oestradiol and progesterone.
[*] In the late luteal phase, FSH and LH remain low but both oestradiol and progesterone titres are high with progesterone the higher.
[*] At the end of the luteal phase progesterone, then oestrogen titres fall, and menstruation begins.
Describe the pattern of secretion of gonadotrophins and gonadal steroids at the beginning of the cycle
[*] Physiological start point: 2-3 days after bleeding. Follicles only partly developed (no ova ready to be released) – follicles secrete very little steroid or inhibin (remember secretion is proportional to development)
[*] Oestrogen, progesterone and inhibin levels are low
[*] GnRH is released from little inhibition at the hypothalamus.
[*] LH and FSH tend to rise, FSH more, as low inhibin levels release FSH from selective inhibin at the anterior pituitary
[*] Then FSH, followed by LH, causes follicles to grow:
- Oestrogen and inhibin secretion rises (FSH stimulates the secretion of inhibin from the granulosa cells. In turn inhibin suppresses FSH)
- FSH secretion is selectively inhibited by inhibin
- Rising oestrogen leads to stimulation of GnRH and hence LH secretion
[*] One follicle normally develops and takes control of the whole cycle.
Describe the pattern of secretion of gonadotrophins and gonadal steroids from days 12-14
About 12-14 days into the cycle
[*] Positive feedback of rising oestrogen tends to stimulate an LH surge
[*] The precise timing of the LH surge may be influenced by environmental factors.
[*] LH surge produces ovulation
[*] Oestrogen levels fall dramatically
[*] Corpus luteum forms spontaneously
After ovulation:
[*] LH promotes oestrogen and progesterone secretion from corpus luteum
[*] As the corpus luteum grows, more steroids are secreted.
[*] Rising oestrogen levels do not exert positive feedback on LH because progesterone levels are also rising
14 days precisely after ovulation:
[*] In the absence of pregnancy, the corpus luteum regresses spontaneously
[*] So progesterone and oestrogen levels dramatically fall
[*] Triggering a menstrual bleed (menses)
[*] And relieving inhibition of FSH and LH, so triggering the development of new follicles and the beginning of a new cycle.
The interval from ovulation to menses is very constant (14 days) however there is variation in cycle length due to variation in timing of ovulation.
Summarize the hypothalamic and pituitary mechanisms underlying cyclical gonadotrophin secretion and the interactions between the ovaries and hypothalamus/pituitary
Overall there is complex interaction between hypothalamus, pituitary and ovary. The durations of the follicular and luteal phases are mainly influenced by the ovary – the time it takes for the follicle to mature, and the lifespan of the corpus luteum respectively. The transition between them is controlled by the brain, via the LH surge.
