Male and female reproductive endocrinology Flashcards
What are the key hormone involves in male reproductive system?
- testosterone
What are the 2 key hormones involved in female reproductive system?
1 - estrogen (most abundant produced by the estrogen)
2 - progesterone
Dihydrotestosterone is an endogenous androgen sex steroid and hormone. This is the metabolised byproduct of which other male hormone?
- testosterone
- conversion of testosterone to dihydrotestosterone occurs in some tissues
Testosterone, estrogen and progesterone all share a similar structure, which makes them all what?
- steroid hormones
- synthesised from cholesterol
What are Leydig cells?
- interstitial cells
- located in interstitial space surrounding the seminiferous tubules in the testes
What are sertoli cells?
- somatic cells (non sex cell: sperm or oocyte)
- located on along lining from capsule to lumen in seminiferous tubules
Spermatogonia are the primordial sperm cells and they are located on the outer edges of the seminiferous tubules. What is the process for the Spermatogonia to become spermatozoa?
- Spermatogonia = diploid cells (1 pair of 23 chromosomes) that undergo mitosis
- Spermatogonia become spermatocytes with 1 full pair of 23 chromosomes, so still a diploid cell
- Spermatocytes undergo meiosis I and II leaving 4 haploid cells (23 chromosomes, but not 1 full pair)
- spermatocytes have then become spermatids, which will mature into spermatozoa
Specifically which part of the hypothalamus secretes gonadotrophin releasing hormone?
- arcuate nuclei neurons
The arcuate nuclei neurons of the hypothalamus secretes gonadotrophin releasing hormone into what vascular plexus system?
- hypophyseal portal vascular system
The arcuate nuclei neurons of the hypothalamus secretes gonadotrophin releasing hormone (GnRH) into the hypophyseal portal vascular system. GnRH then stimulates which cells in the anterior pituitary gland that causes the secretion of which 2 hormones?
- gonadotrophin cells
1 - leutenising hormone (LH)
2 - follicular releasing hormone (FSH)
Leutenising hormone (LH) and follicular releasing hormone (FSH) are both released by the gonadotrophin cells of the anterior pituitary gland in response to gonadotropin releasing hormone. Are they both released at the same rate?
- no
- LH has a cyclical secretion
- FSH has a more stable secretion
In the male reproductive system what effect do luteinizing hormone (LH) and follicle-stimulating hormone (FSH) have on the testes?
- LH binds to Leydig cells and stimulates testosterone secretion
- FSH binds to sertoli cells and increases androgen binding protein production
In the male reproductive system the following occurs in the testes:
- LH binds to Leydig cells and stimulates testosterone secretion
- FSH binds to sertoli cells and increases androgen binding protein (ABP) production
Why is the production of ABP important?
- allows more testosterone to cross the blood testes barrier
- testosterone can then stimulate spermatogenesis
In addition to stimulating spermatogenesis, what other effects does testosterone have?
- androgenic effects
- secondary sexual characteristics in men (facial and body hair growth and voice change, bone and muscle development and metabolism)
In addition to stimulating spermatogenesis and androgenic effects (secondary sexual characteristics in men such as facial and body hair growth and voice change, bone and muscle development and metabolism), testosterone is involved in a negative feedback loop. What happens here?
- high levels of testosterone inhibit further release of gonadotrophin releasing hormone from the hypothalamus
- high levels of testosterone inhibit further release of LH and FSH from the anterior pituitary gland
In addition to stimulating spermatogenesis, what else do the sertoli cells secrete that acts as a negative feedback for the anterior pituitary gland, thus decreasing levels of FH and FSH. What is it that sertoli cells secrete that acts as a negative feedback to the anterior pituitary gland?
- inhibin
- a peptide hormone
What are the 2 hormones involved in the negative feedback loop secreted by leydig and sertoli cells, respectively?
- leydig = testosterone
- sertoli = inhibin
What are the 2 hormones involved in the positive feedback loop are responsible for spermatogenesis?
1 - testosterone
2 - FSH
BOTH STIMULATE SERTOLI CELLS
There is another hormone that is secreted by the placenta, that is essential for the early development of the male reproductive organs during birth. What is this hormone?
- chorionic gonadotrophin hormone (hCG)
What 2 things does testosterone bind with in the blood?
- albumin (low affinity so its in the system quicker)
- sex hormone binding globulin (high affinity for slow release)
When does plasma testosterone and sperm count peak?
- in adulthood
At what age does plasma testosterone and sperm count begin to decrease in adulthood?
- aprox 50 years of age
Testosterone can be converted to what in tissues?
- dihydrotestosterone
if there are excessive levels of testosterone in plasma the liver can convert it into what 2 metabolites prior to excretion?
1 - androsterone
2 - dehydroepiandrosterone
What are the main effects of testosterone in puberty?
- increased body hair
- masculine voice
- increased skin thickness and sebaceous gland secretion (acne)
- increased muscle mass
- increased bone matrix
- increase of the basal metabolic rate
- increase in erythropoiesis
In the ovary what are granulosa cells?
- somatic cell (not sperm or ooycte) located in the ovaries
- form layer around the oocyte, zona pellucida and corona radiata (inwards to outwards)
In the ovary the granulosa cells are somatic cells (not sperm or ooycte) located in the ovaries that form a layer around the zona pellucida and oocyte. What is the function of the granulosa cells?
- secrete oocyte maturation factor to keep oocyte in primordial stage until puberty
- provide nourishment for the developing oocyte to develop from primordial follicle to primary oocyte
What are, and where can theca cells be found?
- endocrine cells
- form a layer around the granulosa cells of the primary oocyte forming a capsule for the follicle
Once gonadotrophin releasing hormone has been released from the hypothalamus and then stimulated the gonadotrophin cells of the anterior pituitary gland, leutenising hormone (LH) and follicular stimulating hormone (FSH) are secreted. Which cells in the ovaries do LH and FSH act on?
- LH = theca and granulosa cells
- FSH = granulosa cells
What are tropic hormones?
- hormones that have other endocrine glands as their target
- LH and FSH are examples of tropic hormones
Once gonadotrophin releasing hormone has been released from the hypothalamus and then stimulated the gonadotrophin cells of the anterior pituitary gland, leutenising hormone (LH) and follicular stimulating hormone (FSH) are secreted. LH and FSH act on the following:
- LH = theca and granulosa cells
- FSH = granulosa cells
Once FSH has stimulated the granulosa cells, that 4 things can these cells then secrete?
1 - estrogen
2 - activin (peptide hormone that stimulates anterior pituitary gland and FSH production)
3 - inhibin (peptide hormone that inhibits anterior pituitary gland and FSH production)
4 - progesterone
Once gonadotrophin releasing hormone has been released from the hypothalamus and then stimulated the gonadotrophin cells of the anterior pituitary gland, leutenising hormone (LH) and follicular stimulating hormone (FSH) are secreted. LH and FSH act on the following:
- LH = theca and granulosa cells
- FSH = granulosa cells
Once LH has stimulated the theca cells, that 2 things can these cells then secrete?
1 - progesterone
2 - androgens
Leutenising hormone (LH) is able to stimulate theca cells, which then release androgens. What then happens to the androgens?
- LH stimulates theca cells to synthesise and secrete androgens
- androgens then move into granulosa cells
- FSH then stimulates granulosa cells to convert androgens into estrogen
In order for a theca and granulosa cells to synthesise and produce progesterone, what else must bind with the theca cells?
- low density lipoproteins (LDL)
- LDL bring cholesterol to the theca cell
What type of receptor is the leutenising hormone receptor on theca and granulosa cells?
- GPCR, specifically Gas
- activate adenylyl cyclase that converts ATP into cAMP
- cAMP then activates protein kinase A
Once LH and LDL has bound to the theca and granulosa cells what is the process of creating progesterone and androgens?
- cholesterole is converted into pregnenolone
- pregnenolone is converted into progesterone
Once progesterone has been created in theca and granulosa cells, all progesterone is moved into the theca cells for what to occur?
- progesterone is converted into androgens
Once progesterone has been created in theca and granulosa cells, all progesterone is moved into the theca cells and converted into androgens. The androgens are then transported to the granulosa cells. What then happens?
- FSH binds to GPCR (Gas) and activates protein kinase A (Pka)
- PKa then activates the enzyme aromatase
- aromatase converts androgens into estrogen
What organic molecule does estradiol, progesterone and testosterone all come from?
- cholesterol
In males, how do excessive levels of testosterone cause a negative feedback loop on the hypothalamus?
- reduces kisspeptin levels (neuroendocrine hormone)
- low kisspeptin will inhibit or reduce the levels of gonadotrophin release hormone (GnRH) released from the hypothalamus
In males, how do excessive levels of testosterone cause a negative feedback loop on the gonadotrophin cells in the anterior pituitary glands?
- inhibit the release of FSH and LH
In males testosterone is able to have a negative feedback effect on the hypothalamus and reduce gonadotrophin releasing hormone (GnRH) through kisspeptin and the anterior pituitary gland and reduce FH and FSH secretion. What other hormone is released from sertoli cells that is able to inhibit FSH release from the anterior pituitary glands?
- inhibin
In females what affect does a low level of estrogen have on hypothalamus, and when would the levels of estrogen be this low?
- low levels of estrogen prior to puberty
- low estrogen levels reduce kisspeptin levels
- low kisspeptin levels reduces GnRH as prior to puberty they are very sensitive
Once a female reaches puberty, do the small levels of estrogen still provide a negative feedback loop that reduces kisspeptin and thus GnRH levels?
- no
- receptors desensitise and need higher levels of estrogen to inhibit
- results in larger amounts of GnRH being released by the hypothalamus
In females, following ovulation what do the granulosa cells of the corpus luteum secrete that is able to have a negative feedback loop on the secretion of FH and FSH?
- inhibin
The theca cells in females will secrete testosterone, which can provide a negative feedback loop on kisspeptin levels and thus GnRH levels from the hypothalamus. However, testosterone can also be moved into another cell and is changed into something else in females. What cell is it transferred into and converted into?
- transferred into granulosa cells from theca cells
- converted from testosterone into estrogen (some is progesterone)
In females estrogen and progesterone generally provide a negative feedback loop that inhibits GnRH release and thus both LH and FSH from the anterior pituitary gland. However, there is once case in a females reproductive cycle, where estrogen levels will rise excessively, which then cause what to happen?
- increase GnRH release from the hypothalamus
- BUT inhibits FSH
- BUT stimulates large amounts of LH
Does the uterus come under the influence of the hypothalamic–pituitary–gonadal axis?
- no
- hormones from ovaries influence the uterus
The theca cells that surround the primary oocyte respond to LH levels by producing testosterone. This testosterone is then transferred to the granulosa cells where it is converted into estrogen. What does the estrogen then do to the theca cells?
- increase the number of LH receptors on theca cells
- more LH receptors means more testosterone and more estrogen
Which hormone is the key driver of primary follicle growth in the female cycle?
- follicular stimulating hormone
How many follicles mature each month?
- just one
Only one follicle matures each month, that is then released through ovulation. What is the process called where other follicle degrade?
- atresia
- suspected negative feedback mechanism
How long does the average female monthly cycle last?
- 28 days
Label the follicle using the labels below”
oocyte corona radiata zona pellucida granulosa cells theca cells
1 = oocyte 2 = zona pellucida 3 = theca cells 4 = granulosa cells 5 = corona radiata
What is the key hormone that ovulation is dependent on?
- leutenising hormone
- this is called the LH surge
What is menstruation?
- period of females cycle where the endometrium sheds and there is loss of blood for around 5-7 days
In days 0-15 and 16-28 of the female cycle, which is higher estradiol or progesterone?
- days 0-15 = estradiol
- days 16-28 = progesterone
What happens to progesterone in plasma that is in excess?
- degraded to other steroids
What are some of the key functions of estrogen in females?
- development of the female reproductive organs In PUBERTY
- enlargement of the uterus and changes in the endometrium (endometrial stroma proliferation and endometrial gland growth) in PUBERTY
- fallopian tube epithelial lining proliferation
- bone growth (through osteoclast inhibition)
- increased subcutaneous fat deposition
- small increase in the basal metabolic rate, small increase in protein synthesis
What are some of the key functions of progesterone in females?
- preparation of the uterus for implantation following ovulation
- increased secretion by the fallopian tubes mucosal lining preparing to move the egg safely to the uterus
How do steroid hormones, such as estrogen and progesterone have their molecular effect on target tissue?
- hydrophobic so bind with proteins such as albumin
- transported to cells/tissue in plasma
- diffuse across cell membrane and bind to a receptor
- receptor/steroid complex is formed
- receptors can then bind to specific genetic sequences, turning it on or off
- on and off genes results in increased or decreased protein synthesis
Steroid hormones, once within the nucleus of the cell do not just randomly bind to DNA, they bind to a specific part. What is this called?
- steroid response element
There are 3 key phases to the female reproductive cycle, which on average lasts 28 days. What are the 3 key stages?
1st = menstrual phase 2nd = proliferative phase 3rd = secretory phase
The endometrium is the most inner layer of the uterus (endo, myo and perimetrium) consists of a single layer of columnar epithelium that rests on the stroma. The endometrium contains 2 important layers, what are these 2 layers called?
1 = stratum basalis (bottom layer)
2 - stratum functionalis
There are 2 special type of artery that is contained within the stratum functionalis, what are they called?
- coiled arteries
- spiral arteries
What is the menstrual phase of the female reproductive cycle, which generally lasts between 0-5 days?
- shedding phase of the endometrium
- specifically the stratum functionalis
The menstrual phase of the female reproductive cycle, which generally lasts between 0-5 days is shedding phase of the endometrium, specifically the stratum functionalis. What are the 2 main components of what is lost within the stratum functionalis?
1 - columnar epithelial cells
2 - coiled and spiral arteries (this is why there is blood during periods)
The menstrual phase of the female reproductive cycle, which generally lasts between 0-5 days is shedding phase of the endometrium, specifically the stratum functionalis. The 2 main components that are lost within the stratum functionalis are columnar epithelial cells and coiled and spiral arteries (this is why there is blood during periods). What is happening to estradiol and progesterone levels during this time?
- both are low
The second phase of the female reproductive cycle is proliferation, which generally occurs between days 5-14. What 2 key things are actually proliferating during this phase and what is the purpose of this?
- stratum basalis (SB) proliferates creating new stratum functionalis layer
- straight arteries in undergo angiogenesis forming coiled and spiral arteries
- prepare the uterus for the fertilised egg
The second phase of the female reproductive cycle is proliferation, which generally occurs between days 5-14. During this phase 2 major things occur:
- stratum basalis (SB) proliferates creating new stratum functionalis layer
- straight arteries undergo angiogenesis forming coiled and spiral arteries
The purpose of the proliferative phase is to prepare the uterus for the fertilise egg. What is the key hormone that is driving the proliferative phase?
- estrogen
Estrogen is the key hormone that drives the proliferative phase of the female reproductive cycle. In addition to performing the following:
- stratum basalis (SB) proliferates creating new stratum functionalis layer
- straight arteries undergo angiogenesis forming coiled and spiral arteries
What else does estrogen drive the formation of in the endometrium?
- uterine glands
Secretion is the final phase of the female reproductive cycle. What days does this generally occur?
- days 14-28
Secretion is the final phase of the female reproductive cycle, occurring on days 14-28. What is the key hormone driving this phase and where is it secreted from?
- progesterone
- corpus luteum produces progesterone
Secretion is the final phase of the female reproductive cycle, occurring on days 14-28. Progesterone is the key hormone driving this phase and it is secreted from the corpus luteum, the left overs following ovulation. What does progesterone do to the thickness of the stratum functionalis and blood vessels in this layer of the endometrium?
- increase thickness of the stratum functionalis
- increase spiral and coiled artery length and increase blood flow
Secretion is the final phase of the female reproductive cycle, occurring on days 14-28. Progesterone is the key hormone driving this phase and it is secreted from the corpus luteum, the left overs following ovulation. What does progesterone do to the uterine glands that were formed during the proliferative phase driven by estrogen?
- signal uterine glands to start producing nutrient rich broth
- in preparation for the fertilised egg
Towards the end of the secretion phase the corpus luteum will undergo involution (shrinking of an organ). What happens to estrogen and progesterone levels, and what does this then signal the beginning of?
- both begin to drop
- endometrium begins involution and vasoconstriction, called menstruation
