4 Flashcards
What is puberty?
- a stage of morphological, physiological and behavioural development when sexual maturation and growth are completed and result in ability to reproduce
- primary sexual characteristics established before birth
- but reproductive system inactive until puberty
Which gender starts and ends puberty first?
Girls
What secondary sexual characteristics develop in girls and when?
- usually around 9 to 13 years
- breast bud (thelarche)
- pubic hair growth (thelarche)
- begins (adrenarche)
- growth spurt
- onset of menstrual
- cycles (menarche)
- pubic hair at end stage (more coarse)
- breasts at end stage
Define primary sexual characteristics
- sexual characteristics at birth (i.e. before puberty has begun)
- includes the anatomy of the internal and external genitalia
Define secondary sexual characteristics
-characteristics that develop after puberty i.e. pubic hair, breast or genital development/enlargement, and menstruation in females
What is thelarche?
- “breast bud” development
- first sign of puberty in girls
What influences the development of pubic hair?
Testosterone in both boys and girls
What is menarche?
Initiation of the menstrual cycle, with a girl’s first period
Describe the secondary sexual characteristics in males
- start at around 10-14 years old
- genital development; testicular volume enlargement
- begin pubic hair growth
- spermatogenesis
- begin growth spurt
- genital enlargement; testes and external male genitalia continue to increase in size and volume until adult external genitalia has developed
- pubic hair; becomes much coarser
What is the tanner scale?
Marks pre-puberty to adult scale
Describe the accelerated somatic growth in both sexes
- occurs in both
- depends on growth hormone, IGF-1, and sex steroids in both sexes
- earlier and shorter in girls
- men larger b/c growth spurt longer and slightly faster
- genital development in boys depends on testosterone
- ended in both sexes by epiphyseal fusion
- oestrogen closes epiphyses earlier in girls
- closing of epiphyseal plates is caused by oestrogen in both sexes
- process is called aromatization and occurs in the periphery tissues
- can convert testosterone into oestrogen in males
Why does puberty occur earlier nowadays?
- Back then average age was 17 but now 13
- in girls, critical weight is 47kg
- if below 47kg then menstrual cycle will cease
- body weight is an important factor: nutrition
- leptin may be involved in signalling
Explain the role of the HPG axis in puberty
- hormonal changes occurs before physical
- puberty initiated by the brain (hypothalamus)
- leptin levels cause the initial stimulation of the hypothalamus to release GnRH
- Nocturnal GnRH pulsatile release happens much earlier before physical changes
- GnRH release causes realease of LH and FSH in the anterior pituitary
- GnRH release from hypothalamus to pituitary is paracrine signalling
- LH and FSH release from pituitary to gonad is endocrine signalling
- FSH and LH stimulate Gonads to release oestrogen and androgens which drive the development of secondary Sertoli cells
Even though most parts of the reproductive system can work before normal puberty age, why dont they?
- low GnRH secretion
- not a substantial amount of the needed hormones
How can we remember the influence of FSH and LH on the genitalia anatomy?
Male
- Sertoli cells produce Sperm under the influence of fSh
- Leydig cells produce testosterone under the influence of Lh
Female
- granuloSa cells respond to fSh
- tHeca cells respond to lH
What are the characteristics of GnRH?
- secretion in pulses tied to internal biological clock (synchronized by external signal i.e. by 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 its own receptor
What environmental factors influence puber
- breeding is seasonal
- new “puberty” each year
- triggered by changes in day length
- involvement of pineal gland
- secretion of melatonin
- pineal tumours can influence puberty in humans (pernicious puberty)
- leptin important for sustaining reproduction
What is the GnRH-1 gene
- lack of this gene results in no puberty
- primarily responsible for mammalian GnRH
- GnRH-1 gene exclusively expressed in discrete population of neurons in the hypothalamus
- treating prepubertal primates with pulsatile GnRH alone induces puberty
- lack of gonadotrophin synthesis and secretion and reproductive development occurs if GnRH is BLOCKED
- treatment of infertile male HPG-mice with synthetic GnRH induces spermatogenesis and in females similar treatment causes ovarian maturation and can lead to established pregnancy
- therefore critical role of GnRH in reproductive maturation established
What is adenohypophysis (aka AP)
- aka anterior pituitary
- not nervous tissue
- connected to the hypothalamus by superior hypophyseal artery
- an amalgam of hormone producing glandular cells
- AP produced 6 hormones: prolactin, GH, TSH, ACTH, FSH, LH
- FSH, LH and prolactin most significant for reproduction
How does GnRH affect the anterior pituitary?
- secretion of gonadotrpin-releasing hormone (GnRH) by the hypothalamus stimulates the AP gland gonadotrophs to secrete two gonadotropic hormones: FSH and LH
- one releasing hormone: GnRH is a 10 AA peptide
- GnRH release is pulsatile
- released every 1-3 hours
- intensity of GnRH stimulus is affected by frequency and intensity of release
- GnRH travels to pituitary hypophysial portal system
Explain how LH and FSH increase during puberty
- in young children, LH and FSH levels are insufficient to initiate gonadal function
- between 9-12 years, blood levels of LH and FSG increase in pulses
- amplitude of pulses increases, especially during sleep (nocturnal activity)
- high levels of LH and FSH initiate gonadal development
Explain the sleep dependent nocturnal rise in LH
- in adolescent boys the sleep related LH increase
- stimulates a nocturnal rise of testosterone
- androgen levels increase could account for some of the early pubertal changes seen in males
- similar pattern seen in females with concomitant (accompanied) increase in oestrogen
Explain the negative feedback system between the AP and hypothalamus in regards to androgens and oestrogen
- hypothalamus produces GnRH
- GnRH causes pituitary to produce LH and FSH
- LH and FSH causes gonads to produce androgens and oestrogen
- androgens and oestrogens negatively act on the hypothalamus, preventing production of GnRH
- in turn halts the whole cycle
Explain androgen production in males
- LH stimulates Leydig cells in testis
- produce steroid hormone (from cholesterol): testosterone
- greatest amount produced from testis
- once production starts in the medium, long term testosterone levels remain constant (doesn’t change for a long time)
- there is an effect of circadian rhythm (levels highest in the early morning)
- effects of environmental stimuli (both driven by brain)
How do the testes produce testosterone?
-each lobule contains 1-4 tightly coiled tubules which are seminiferous tubules (ST)
-each ST is about 60cm long
90% of the testicular volume
Location for spermatogenesis
-ST cannot function without Leydig cells
-in between ST there is loose CT and blood vessels
-interstitial tissue contains interstitial cells (Leydig cells)
-LEydig cells produce testosterone
-they function independently of ST
Describe the seminiferous tubule cells
-ST lined by complex epithelium made of 2 cell types
-Supporting cells (Sertoli cells)
-spermatogenic cells/germ cells
Sertoli cells
-provide nutrition and hormonal support to germ cells allowing sperm formation
-sensitive to FSH (increase sperm production)
-secreted inhibin (-) feedback on AP FSH
-Sertoli cells sensitive to FSH and act on negative feedback
-sometimes messed up sperm is made which we do not want in the ECF
-so double layer of cells helps to prevent that
How does FSH and LH act on females?
- acts primarily on gonads via Gas PCR to adenylyl earth cyclase
- female: target cells, ovarian granulose cells, theca interna cells
- stimulates sex hormone synthesis (steroidgenesis)
- i.e. oestrogen, progesterone, inhibin
- controls gamete production (folliculogenesis and ovulation)
- granulosa cells respond to FSH
- theca cells respond to LH
What in the follicle releases progesterone?
Corpus luteum
How does oestrogen and progesterone on GnRH?
- moderate titres of oestrogen reduce GnRH secretion (negative feedback)
- high titres of oestrogen alone promote GnRH secretion (positive feedback, LH “surge”)
- LH surge: starts of as small concentration of oestrogen then surges to high concentration
- small amount of oestrogen negatively feedbacks on GnRH
- high concentration of oestrogen will increase GnRH (positive feedback)
How does oestrogen and progesterone act on FSH and LH?
- progesterone increases inhibitory effects of small amounts of oestrogen
- progesterone prevents positive feedback of high oestrogen (no LH surge)
- oestrogen reduces GnRH per pulse, progesterone frequency of pulses
How does inhibin act on FSH?
- comes from granulose cells of corpus luteum
- inhibits the secretion of FSH (same as male)
- has a small inhibitory effect on LH
What hormonal changes do you see in a growth spurt?
- GH secretion from pituitary
- increases TSH
- increases metabolic rate
- promotes tissue growth
- increase of androgens= retention of minerals in body to support bone and muscle growth
- therefore you get growth spurt
- IGF also helps with somatic growth
What is the significance of leptin in puberty?
- signalling molecule regarding energy
- signals the median eminence for GnRH
- leptin is an adipocyte-derived protein hormone
- signals information about energy stores to CNS
- important role in regulating neuron doctrine function
- reproductive dysfunction associated with leptin deficiency
- leptin can accelerate the onset of reproductive function
- leptin has pulsatile release pattern significantly associated with the variations of LH
- leptin can regulate GnRH levels, and its secretion may, in turn, be influenced by gonadal steroids but appears to be independent of LH control
How does control of reproduction differ in males and females?
- Male: continuous gamete production required
- Female:
- tract needs to prepare for implantation
- need to build in a “waiting phase”
- therefore gamete production needs to be periodic so that gamete can be nurtured and developed
What is the hypothalamus-pituitary-ovary axis?
- the female system
- There is a cycle rather than continuous production of gametes
- feedback is positive and negative depending on the stage of the cycle
- GnRH produced by hypothalamus
- acts on AP to release LH and FSH
- gonadotrophins act on ovary to promote follicular development and to produce ovarian hormones such as steroid hormones and inhibin
- controlled by effects of gonadal hormones positively and negatively
How does the feedback of the hormones differ in males and females?
Male
-LH and FSH release causes increase of testosterone levels
-high levels of testosterone will have an inhibitory effect on the hypothalamus and anterior pituitary
Female
-small amounts of oestrogen or progesterone will cause a negative effect
-large amounts of oestrogen or progesterone will have a positive effect
Describe the menstrual cycle
- divided into ovarian and uterine cycle
- preparation of the gamete (ovarian)
- preparation of the endometrium (uterine)
- ovulation: release of the gamete
- waiting: pause, maintaining the endometrium until a signal is received to indicate that fertilization has happened
How is the menstrual cycle controlled?
- gonadotrophins: act on the ovary
- ovarian steroids: act on tissues of the reproductive tract, act to control the cycle
Why is the pulsatile GnRH release so important?
- intermittent GnRH receptor is an absolute requirement for fertility
- if GnRH receptors are exposed to continuous presence of GnRH then the receptors become desensitized
- as a result FSH and LH production stops
- which in turn results in Gonadal steroid production stopping
What is endometriosis and how can we treat it?
- when lining of the uterus grows in other places such as Fallopian tubes, ovaries or along the pelvis
- treatment: give GnRH agonist to relieve symptoms and pause cycle
What two parts can we separate the ovarian cycle into?
Follicular phase and luteal phase
Describe the follicular phase
- start of the cycle
- no ovarian hormone production
- early development of follicles begins
- low steroid and inhibin levels
- little inhibition at the hypothalamus or AP
- free from inhibition since no hormones to inhibit
- FSH levels start to rise
- as FSH rises it causes the number of granulosa cells to increase
- also causes development of the theca interna and externa cells
- follicle now capable of oestrogen secretion and these low levels will cause negative feedback at hypothalamus and AP
- inhibin secretion begins
What happens in the mid-follicular phase?
- a dominant follicle must be nominate in order to prevent recruitment of any further follicles
- dominant follicle known as the Graafian follicle with a large antrum, ready to be released at ovulation
- as follicle develops oestrogen levels increase
- can now exert a positive feedback on hypothalamus and AP
- as a results GnRH levels rise which causes LH to rise NLY
- as follicle develops, inhibin also rises to prevent FSH stimulating more than one dominant follicle
What are theca interna and theca externa cells?
-make up the outer layer of the follicle
What hormone changes occur in preparation for ovulation?
- circulating oestradiol and inhibin rise rapidly
- oestradiol production is no longer dependent on FSH
- surge in LH production
- progesterone production begins as granulose cells become responsive to LH
- modulation of GnRH pulse generator
What is the LH surge?
- when there is a rapid increase in the amount of LH
- high concentrations of oestradiol enhances sensitivity of AP gonadotrophs to GnRH
- occurs in late follicular phase
- key factor that drives ovulation
What happens at ovulation?
- meiosis 1 completes and meiosis 2 starts
- mature oocyte extruded through the capsule of the ovary
What are the effects of LH after ovulation?
- follicle is lutenised
- secretes oestrogen and progesterone in large quantities
- inhibin continues to be produced
- but LH is now also suppressed because of negative feedback due to the presence of progesterone
- further gamete development suspended (waiting phase established)
Describe the luteal phase
- happens after ovulation
- waiting stage to see if fertilization and implantation occurs
- lutein=yellow in regards to corpus luteum
- function of corpus luteum is to produce progesterone and oestrogen from androgens
- produces inhibin
- promotes production of progesterone
- regresses spontaneously in the absence of a further RISE in LH
- high levels of oestrogen will cause a positive feedback but the high levels of progesterone causes a NEGATIVE feedback on oestrogen at hypothalamus and AP
How long is the luteal phase and why?
- typically 14 days because lifespan of corpus luteum is 14 days
- without implantation, corpus luteal regresses and levels of oestrogen, progesterone and inhibin drop allowing the cycle to start again
What two phases is the uterine cycle split into?
Proliferative phase and secretory phase
Describe the uterine cycle
- lining of the uterus, endometrium, is responsive to hormones produced by the ovary
- endometrium is a specialized epithelium
- responds to oestrogen by proliferating
- responds to oestrogen and progesterone by secreting
Describe the proliferative phase
- myometrium is the muscular wall of uterus
- endometrium is the epithelial lining of the uterine cavity
- endometrium has a functional and basal layer
- at start of cycle endometrium will proliferate and thicken in response to oestrogen produced by the ovary
- simple, straight glands within the endometrium but as this part of the cycle continues and the endometrium continues to develop, the gland becomes coiled and the functional layer doubles in size
- early proliferative: glands sparse and straight
- late proliferative: functional layer has doubled, glands now coiled
- phase caused by oestrogen
Describe the function of the functional and basal layer in the endometrium
- functional layer: sheds during menstruation
- basal layer: allows the regrowth at the start of a new cycle, never sheds
Describe the secretory phase
- occurs after ovulation
- under influence of progesterone
- when hormones from corpus luteum begin to fall, glands lose their structure and the endometrium becomes ready to shed its functional layer if implantation has not occurred
- early secretory: endometrium is at max thickness, very pronounced coiled glands
- late secretory: glands adopt characteristic “saw tooth” appearance
What happens at the end of the uterine cycle if implantation doesn’t occur?
- in the absence of a further rise in LH, corpus luteum regresses
- dramatic fall in gonadal hormones
- relieving negative feedback
- resets to start again
What happens if ferilisation does occur?
- after 14 days, HCG will be produced by the synctiotrophoblast
- acts the same as LH
- will maintain the corpus luteum
- will in turn maintain the pregnancy by producing oestrogen and progesterone
- eventually placenta will take over this function
What are the actions of oestrogen in the follicular phase?
- Fallopian tube function
- thickening of endometrium
- growth and motility of myometrium
- thin alkaline cervical mucus
- vaginal changes
- changes in skin, hair, metabolism
What are the actions of progesterone in the luteal phase?
- further thickening of endometrium into secretory form
- thickening of myometrium, but reduction of motility
- thick, acid cervical mucus
- changes in mammary tissue
- increased body temperature
- metabolic changes
- electrolyte changes
What the normal duration for the cycle?
21-35 days
What factors affect the menstrual cycle?
- physiological factors (pregnancy, lactation)
- emotional stress
- low body weight
