Neuroendocrinology Flashcards
Describe the secretory pathway of reproductive hormones
GnRH acts on the anterior pituitary, and triggers the secretion of LH. LH acts on the ovaries to trigger ovulation, or testes to trigger testosterone secretion and spermatogenesis
Define hormonal stimulus
A hormone is released into the bloodstream - regulates either the activity of target organ, or triggers the release of another hormone
How is hormone secretion regulated?
Regulated by signals from nervous system, chemical changes in the blood or by other hormones
Negative feedback control (most common):
- decrease/increase in blood level is reversed
Positive feedback control:
- the change produced by the hormone causes more hormone to be released
Disorders involve either hyposecretion or hypersecretion of a hormone
Describe the features of negative feedback systems for reproductive hormones (male)
Hypothalamus produces GnRH, which stimulates the anterior pituitary, which produces LH and FSH. FSH acts upon the testis to initiate spermatogenesis, and LH acts upon the Leydig cells to initiate the production of testosterone. Testosterone then inhibits the release of LH and FSH, and also inhibits the release of GnRH
Describe the structure and features of the Pituitary Gland
Two-lobed organ that secretes nine major hormones
Neurohypophysis: Posterior lobe (neural tissue) & the infundibulum
Receives, stores, & releases hormones from the hypothalamus
Adenohypophysis: Anterior lobe
Made up of glandular tissue
Synthesizes and secretes a number of hormones
Describe the features of the posterior lobe of the pituitary gland
The posterior lobe is a down-growth of hypothalamic neural tissue
Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract)
Nuclei of the hypothalamus synthesize oxytocin & antidiuretic hormone (ADH)
These hormones are transported to the posterior pituitary
Describe the features of the anterior lobe of the pituitary gland
The anterior lobe of the pituitary is an out-pocketing of the oral mucosa
There is no direct neural contact with the hypothalamus
There is a vascular connection, the hypophyseal portal system, consisting of:
The primary capillary plexus
The hypophyseal portal veins
The secondary capillary plexus
Describe the function of the adenohypophysis
The hypothalamus sends a chemical stimulus to the anterior pituitary:
Releasing hormones stimulate the synthesis & release of hormones
Inhibiting hormones shut off the synthesis & release of hormones
Name the two major gonadotropins
Follicle stimulating hormone (FSH) Luteinizing hormone (LH)
When are the gonadotropins released?
They are released from the anterior pituitary in response to the secretion of GnRH
What are the functions of gonadotropins?
Regulate the function of the ovaries and testes
FSH stimulates gamete (egg or sperm) production
Absent from the blood in prepubertal boys & girls
Triggered by hypothalamic gonadotropin-releasing hormone (GnRH) during & after puberty
When do the levels of gonadotropins rise?
Puberty
What are the functions of FSH?
Initiates the formation of follicles within the ovary
Stimulates follicle cells to secrete estrogen
Stimulates sperm production in testes
What are the cells that releases gonadotropins?
Gonadotrophs
What is the function of LH in females?
Secretion of oestrogen
Ovulation of 2nd oocyte from ovary
Formation of corpus luteum
Secretion of progesterone
What is the function of LH in males?
Stimulates interstitial cells to secrete testosterone
What is the function of gonadotropins in females?
LH works with FSH to cause maturation of ovarian follicle
LH works alone to trigger ovulation (expulsion of egg from follicle)
LH promotes synthesis & release of oestrogens & progesterone
Describe the hormonal regulation of the female reproductive cycle
GnRH secreted by the hypothalamus controls the female reproductive cycle:
Stimulates anterior pituitary to secrete FSH & LH
FSH initiates growth of follicles that secrete estrogen
Oestrogen maintains reproductive organs
LH stimulates ovulation & promotes formation of the corpus luteum which secretes estrogens, progesterone, relaxin & inhibin
Progesterone prepares uterus for implantation and the mammary glands for milk secretion
Relaxin facilitates implantation in the relaxed uterus
Inhibin inhibits the secretion of FSH
Why does the secretion of FSH need to be inhibited during pregnancy?
If ovulation continued once pregnancy had occurred, there is a risk of a second ovum being fertilised, and the second ovum may not be able to implant in the uterus, and so would implant in the fallopian tubes, which would risk the life of the mother.
The presence of inhibin inhibits FSH, and so prevents multiple pregnancies at different stages of development occurring.
What is the function of progesterone?
Progesterone prepares uterus for implantation and the mammary glands for milk secretion
What is the function of relaxin?
Relaxin facilitates implantation in the relaxed uterus
What is the function of inhibin?
Inhibin inhibits the secretion of FSH
What is the function of oestrogen?
Promote development and maintenance of female reproductive structures, feminine secondary sex characteristics, and breasts
Increased protein anabolism
Lower blood cholesterol
Moderate levels inhibit release of GnRH, FSH and LH
How is the activity of the adenohypophysis controlled?
The hypothalamus sends a chemical stimulus to the anterior pituitary:
- Releasing hormones stimulate the synthesis & release of hormones
- Inhibiting hormones shut off the synthesis & release of hormones
Describe the LH surge
LH is normally released in a pulsatile manner. For the majority of the cycle, this is what is occurring, with negative feedback being provided by oestrogen.
However, in the pre-ovulation phase, oestrogen provides positive feedback, producing a rapid release of GnRH and then LH.
What are the different phases of the female reproductive cycle?
⦁ Menstrual phase
⦁ Preovulatory phase
⦁ Ovulation
⦁ Postovulatory phase
How does FSH affect ova?
Stimulates them to become primordial follicles
What are primordial follicles?
Follicles that can, with the appropriate stimulation or environment, develop into fully developed ovarian follicles, which can then ovulate and release ova.
What happens to primordial follicles, under the stimulation of FSH?
They are converted into primary follicles
What triggers the process of ovulation?
LH surge
What occurs during ovulation?
Ovum is released, and collected by the fimbriae of the fallopian tubes, and is moved down the tube, where it may be fertilised.
When an ovum is released, what structure is left behind in the ovary?
Corpus hemorrhagicum
Why is the Corpus hemorrhagicum important?
It develops into the corpus luteum, which produces progesterone and oestrogen, which cause the lining of the uterus to become even thicker, and develop more blood vessels in its lining
If the ovum does not become fertilised, what happens to the corpus luteum?
It begins to die, reducing the amount of progesterone and oestrogen produced
What happens when levels of progesterone and oestrogen drop to low levels after the corpus luteum begins to die?
The process of menstruation begins
Describe what occurs during the menstrual phase of the female cycle
Menstruation lasts for 5 days
First day is considered beginning of 28 day cycle
In ovary:
20 follicles that began to develop 6 days before are now beginning to secrete estrogen
Fluid is filling the antrum from granulosa cells
In uterus:
Declining levels of progesterone caused spiral arteries to constrict – glandular tissue dies
Stratum functionalis layer is sloughed off along with 50 to 150 ml of blood
Describe what occurs during the pre-ovulatory phase of the female cycle
Lasts from day 6 to 13 (most variable timeline)
In the ovary (follicular phase):
Follicular secretion of estrogen & inhibin has slowed the secretion of FSH
Dominant follicles survives to day 6
By day 14, graafian follicle has enlarged & bulges at surface
Increasing estrogen levels trigger the secretion of LH
In the uterus (proliferative phase):
Increasing estrogen levels have repaired & thickened the stratum functionalis to 4-10 mm in thickness
Describe what occurs during ovulation
Oestrogen stimulates the release of GnRH, which stimulates the release of even more LH (LH surge), which triggers the rupture of the follicle, and release of second oocyte (around day 14).
Corpus hemorrhagicum results.
Describe what occurs during the postovulatory phase
Most constant timeline = lasts 14 days
In the ovary (luteal phase):
If fertilization does not occur, corpus albicans is formed as hormone levels drop, secretion of GnRH, FSH & LH rises
If fertilization does occur, developing embryo secretes human chorionic gonadotropin (hCG) which maintains health of corpus luteum & its hormone secretions
In the uterus (secretory phase):
Hormones from corpus luteum promote thickening of endometrium to 12-18 mm
Formation of more endometrial glands & vascularization
If no fertilization occurs, menstrual phase will begin
What regulates the HPG Axis?
The secretion of GnRH from the hypothalamus
What is the signal that causes the elevation in plasma levels of LH which leads to ovulation?
Increase in GnRH secretion
Where are the control centres that regulate the HPG Axis found?
In the hypothalamus
Why is the medial pre-optic area proposed as a control centre of the HPG Axis?
Rich in GnRH producing neurones
Release their hormone at the median eminence
Receive inputs from higher centres in the brain
What are the environmental factors that can affect the menstrual cycle?
Photoperiod
Stress
Nutritional status
How do environmental factors affect the menstrual cycle?
By affecting the release of GnRH
What are the two modes of GnRH secretion in the female?
Pulsatile mode
Surge mode
How does the feedback mechanism from oestrogen change during pulsatile and surge modes?
Negative feedback during pulsatile mode
Positive feedback during surge mode
Describe the features of pulsatile GnRH secretion
Drives tonic gonadotropin release
Greater part of ovarian cycle
Regulates folliculogenesis and the corpus luteum
Negative regulation by oestrogen
Describe the features of surge GnRH secretion
Generates pre-ovulatory LH surge
Triggers ovulation
Positive regulation by oestrogen
Describe the experimental evidence that proves the relation between the GnRH and LH surges
Moenter et al, 1992
GnRH and LH levels monitored in female sheep that were given hormones to mimic the surge portion of the hormonal cycle
Shows GnRH surge, followed LH surge. Demonstrates that GnRH stimulates LH release
Why were sheep used in GnRH and LH experiments?
Size - easier to obtain blood samples, higher amounts of hormone concentrations compared with smaller animals
Sheep can also be trained to come into a pen during different times of the day, so blood samples can be taken
What experiment first demonstrated that LH was released in a pulsatile manner?
Knobil and colleagues (Dierschke et al, 1970) showed pulsatile LH release in Rhesus monkeys
What experiment first demonstrated that GnRH was released in a pulsatile manner?
Knobil, 1980
Blood taken from the hypohyseal portal system of sheep, and GnRH measured
What were the results GnRH experiment done by Knobil, 1980?
Showed pulsatile GnRH release
Lesions in hypothalamus: stops menstruation
Administration of GnRH: restores menstruation
Too much GnRH: LH levels rise too much, negative feedback suppresses LH
Implies that menstrual cycle can be controlled entirely by pulsatile GnRH
Since then, pulsatility has been found in other species.
Controlled/fine tuned by negative feedback of gonadal steroids
How was multi-unit activity measured? (Knobil, 1980)
A very large electrode is placed into the mediobasal hypothalamus of the experimental subject (Rhesus monkey). Recordings of the activity of the mediobasal hypothalamus are made over a period of time. Showed that when there is an increase in MUA, it corresponds to pulses of LH being released.
What did the MUA study in sheep (Caraty et al, 1998) show?
Showed that LH pulse stimulated by GnRH pulse
What happens to MUA during LH surge?
MUA disappeared during LH surge (Knobil et al, 1981):
Proved that mechanism for surge must be different from the pulse generator mechanism
What did Ordog et al, 1998 show?
MUA activity in the mediobasal hypothalamus, which stops when the LH pulse is released
What did Herbison, 1998 show?
GnRH cells do not possess any classical oestrogen receptors (E2a)
What did Hrabowvky et al, 2001 show?
Some GnRH cells do have beta-type oestrogen receptors, but beta-type receptors are not involved in regulating reproductive function
