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Hypothalamo-Pituitary-Ovarian Axis
A way of describing the HYPOTHALAMUS, PITUITARY GLAND, and OVARY as one single system, and examining the effects of these individual endocrine glands as they behave in cooperation and regulate one another. 

Fluctuations of hormones
(1) A way of describing the HYPOTHALAMUS, PITUITARY GLAND, and OVARY as one single system,

(2) and examining the effects of these individual endocrine glands as they behave in cooperation (+/- feedback) and have various local and widespread effects.
Hypothalamus Location
Hypothalamus (H) = relatively small structure that lies midcentral in base of brain. Divided into halves by 3rd ventricle (forms ventral and lateral walls of 3rd ventricle). 

A portion of H (medio-basal H) sits above the pituitary.
Hypothalamus (H) = relatively small structure that lies midcentral in base of brain. Divided into halves by 3rd ventricle (forms ventral and lateral walls of 3rd ventricle).

A portion of H (medio-basal H) sits above the pituitary.
m
Hypothalamus Structure & Regions
The H has clusters of neurons, collectively called NUCLEI (which secrete peptide hormones important for controlling pituitary activity).

Neuron cell bodies are located in regions of H; include (1) PRE-OPTIC AREA, and (2) MEDIO-BASAL H
The H has clusters of neurons, collectively called NUCLEI (which secrete peptide hormones important for controlling pituitary activity).

Neuron cell bodies are located in regions of H; include (1) PRE-OPTIC AREA, and (2) MEDIO-BASAL H
m
Hypothalamus Hormone Secretion
H neuron clusters (NUCLEI) secrete peptide hormones which control pituitary activity.

These peptides (A) move to pituitary DIRECTLY by passage through the axons of neurons, OR (B) by a VASCULAR-PORTAL SYSTEM.
Pituitary Gland Structure
Two parts; (1) NEUROHYPOPHYSIS (aka Posterior Pituitary); which is connected to H

(2) ADENOHYPOPHYSIS (aka Anterior Pituitary); distinct, NOT directly connected to H
Two parts; (1) NEUROHYPOPHYSIS (aka Posterior Pituitary); which is connected to H

(2) ADENOHYPOPHYSIS (aka Anterior Pituitary); distinct, NOT directly connected to H
Hypothalamus Functions (5)
Integration of... (1) Nervous System
(2) Endocrine System (including reproduction)
(3) Environmental factors (temp, daylight)
(4) Disease factors (stress, infection)
(5) Nutrition
GnRH neurons
GnRH cell bodies = located in several parts (NUCLEI) of H. GnRH neuron fibers end in MEDIAN EMINENCE near capillary loops of portal vessels. 

Neurons release GnRH into pituitary portal blood supply, which is transported to anterior pituitary cells.
GnRH cell bodies = located in several parts (NUCLEI) of H. GnRH neuron fibers end in MEDIAN EMINENCE near capillary loops of portal vessels.

Neurons release GnRH into pituitary portal blood supply, which is transported to anterior pituitary cells.

Neurotransmitters (VIP, dopamine, seratonin) can modify GnRH release from GnRH neuron fibers.
Pituitary Portal Blood Supply
Pituitary portal blood picks up releasing factors and neurotransmitters secreted by neurons from the median eminence and transports them to anterior pituitary cells.
GnRH
GnRH (aka decapeptide) = Very rapid metabolization due to small size. Short half life (2 - 4 minutes) in blood, making it difficult to measure in systemic circulation.

GONADOTROPE CELLS w/in AP respond to GnRH by producing and secreting LH & FSH.

Mutation to produce or respond to GnRH (w/out GnRH receptor on gonadotroph cells) = infertile. Can provide endogenous GnRH (from organism) / GnRH analogues (slightly modified structure) to restore fertility to individuals who can't produce GnRH.
GnRH Release
GnRH is secreted in PULSATILE fashion. (Given continuously, will suppress gonadotroph cells instead.)

Varying frequency and amplitude depending on (1) species, (2) sex, (3) reproductive stage or stage of cycle in female.

Regulated by (A) systemic (s
GnRH is secreted in PULSATILE fashion. (Given continuously, will suppress gonadotrope cells instead.)

Varying frequency and amplitude depending on (1) species, (2) sex, (3) reproductive stage or stage of cycle in female.

Regulated by (A) systemic (steroids; estradiol, progesterone) and (B) local factors (neurotransmitters in median eminence)
Gonadotrope Cells
Located w/in ANTERIOR PITUITARY. Contains membrane bound GnRH receptor.

GnRH = released into portal circulation around AP. Binding of GnRH (to G-protein coupled GnRH receptor) induces gonadotropin secretion (if GnRH is pulsatile and sufficient amplitude). Down-regulation of GnRH receptors if continuous GnRH binding: then no stimulation of gonadotropin secretion.

Gonadotrope cells synthesize 2 gonadotrophins; (1) LH, and (2) FSH & store in SECRETORY GRANULES.
Anterior Pituitary
The anterior pituitary contains receptors to respond to a variety of releasing factors; Stimulatory hypothalamic hormones; (1) GnRH, (2) CRF, (3) TRH, (4) GHRH, and Inhibitory hypothalamic hormone (5) Dopamine.

AP contains (1) gonadotrope cells; releas
The anterior pituitary contains receptors to respond to a variety of releasing factors; Stimulatory hypothalamic hormones; (1) GnRH, (2) CRF, (3) TRH, (4) GHRH, and Inhibitory hypothalamic hormone (5) Dopamine.

AP contains (1) gonadotrope cells; release FSH/LH, (2) corticotroph cells; release ACTH, (3) thyrotroph cells; release TSH, (4) somatotropic cells; release GH, (5) lactotroph cells; release prolactin.
Gonadotrophins; LH & FSH
Lutenizing Hormone (LH) & Follicle Stimulating Hormone (FSH), are heterodimeric (2 chains) glycoproteins (have CHO chains). 

Alpha chain; shared by LH & FSH (& other gonadotroph hormones) is important but not specific. 

Beta chain; contains branchin
Lutenizing Hormone (LH) & Follicle Stimulating Hormone (FSH), are heterodimeric (2 chains) glycoproteins (have CHO chains).

Alpha chain; Achieves close association w/ receptor. Shared by LH & FSH (& other gonadotroph hormones) is important but not specific.

Beta chain; Contains branching CHO's and acid (which influences 1/2 life & causes to be more or less active). Beta chain is specific to target/receptor.
Relationship b/w GnRH and LH
GnRH acutely induces LH release fm stored granules. LH release = pulsatile, mimics GnRH (close association w/ GnRH pulses). 

GnRH chronically induces LH synthesis 2 replenish stores w/in gonadotroph cells.

To modify LH secretion, can (1) modify GnRH
GnRH acutely induces LH release fm stored granules. LH release = pulsatile, mimics GnRH (close association w/ GnRH pulses).

GnRH chronically induces LH synthesis 2 replenish stores w/in gonadotroph cells.

To modify LH secretion, can (1) modify GnRH secretory pattern, or (2) GnRH receptors on gonadotrope cells.
Relationship b/w GnRH and FSH
FSH is released as soon as it is synthesized (small amounts stored in granules).  FSH release favors GnRH present (low frequency pulse profile).

FSH release  in general doesn't depend on GnRH unless there is a big surge, then its release (from stored g
FSH is released as soon as it is synthesized (small amounts stored in granules). FSH release favors GnRH present (low frequency pulse profile).

FSH release in general doesn't depend on GnRH unless there is a big surge, then its release (from stored granules) follows surge.
FSH releasing factors (other than GnRH)
Other factors important in regulating FSH (besides GnRH) = (1) estradiol, or (2) peptides of the inhibin family. These factors can be secreted from the ovary or locally synthesized w/in the pituitary.

There may be distinct (3) FSH-releasing factor from hypothalamus.

May also modify FSH synthesis/release by modifying (a) GnRH pulsatility, (b) GnRH receptors, (c) secretion of systemic or intrapituitary FSH-regulatory factors.
Ovary
Prod'n of (1) ova, and (2) sex hormones.

In response to gonadotrophins FSH & LH, ovary is involved w/ (1) secretion of estradiol, peptide factors, progeserone & androgens from follicles, and (2) Progesterone fm CL.
Gonadal Steroid Hormones
(1) Impt to maintain pregnancy, 
(2) Prepare repro. tract (for sperm transport/storage, fertilization, embryo transport, embryo survival and implantation, maintenance of pregnancy), 
(3) Estrous behavior, 
(4) Preparation of Mammary gland for lactation
(1) Impt to maintain pregnancy,
(2) Prepare repro. tract (for sperm transport/storage, fertilization, embryo transport, embryo survival and implantation, maintenance of pregnancy),
(3) Estrous behavior,
(4) Preparation of Mammary gland for lactation.
Cow Reproductive Life
Cow; Puberty = 7 - 18 months
NON-SEASONALLY POLYESTROUS; continuous cycles unless pregnant, lactating, or some sort of disease.
Reproductively Cyclic vs. Acyclic
CYCLIC; estrous or menstrual cycles

ACYCLIC; (1) Prepubertal anestrus (haven't reached puberty yet), (2) Postpartum anestrus (onset of lactation), (3) Pregnancy.
Stages of Estrous Cycle (COW)
(COW)
(1) LUTEAL PHASE; Lasts fm time of ovulation until regression (LUTEOLYSIS) of CL, near end of estrous cycle. Involves formation of CL, progesterone prod'n, & luteolysis. 
 
(2) FOLLICULAR PHASE; Initiated after luteolysis, reduction in progestero
(COW)
(1) LUTEAL PHASE; Lasts fm time of ovulation until regression (LUTEOLYSIS) of CL, near end of estrous cycle. Involves formation of CL, progesterone prod'n, & luteolysis.

(2) FOLLICULAR PHASE; Initiated after luteolysis, reduction in progesterone (removing neg. feedback on H) increased GnRH & subsequent LH/FSH release, promoting follicular development & prod'n estrogen

*Then OVULATION separating the two phases.
Reproductive Hormone Feedbacks
(a) LH & FSH; POSITIVE FEEDBACK on ovary

(b) Progesterone & estradiol release from ovary; NEGATIVE FEEDBACK on hypothalamus, inhibiting GnRH release/suppressing pulse frequency of GnRH (leading to less LH & FSH & less positive feedback on estradiol & p
(a) LH & FSH; POSITIVE FEEDBACK on ovary

(b) PROGESTERONE, during luteal phase, released from ovary; NEGATIVE FEEDBACK on hypothalamus, decreasing GnRH pulse frequency (leading to less LH & FSH & less positive feedback on estradiol & progesterone production)

(c) ESTRADIOL (in presence of progesterone, during luteal phase); NEGATIVE FEEDBACK on... (1) hypothalamus, decreasing GnRH amplitude, and (2) pituitary, suppressing synthesis of FSH.

(d) ESTRADIOL from ovary (on its own, w/out Progesterone) = POSITIVE FEEDBACK on... (1) hypothalamus, induce GnRH surge, and (2) pituitary, increases # GnRH receptors for gonadotrophin surge

(e) INHIBIN (an ovarian peptide) from ovary; NEGATIVE FEEDBACK on anterior pituitary, inhibit FSH.
Revision: If you immunize against GnRH, you will get increased estradiol levels in blood (T/F) ?
FALSE.

If immunize, get anti-GnRH antibodies, induce antibody response, inhibit GnRH. GnRH leads to positive feedback of LH/FSH, and positive feedback of estradiol. So...without GnRH, estradiol levels would decrease.
Revision: If you castrate (remove gonads) a female animal, you will get increased levels of FSH in blood?
TRUE.

Removing ovaries = removing negative feedback on hypothalamus and anterior pituitary. Therefore, without estradiol/progesterone/inhibin production, FSH levels will likely increase.
Revision: Gonadal steroids are responsible for estrous cyclicity, ensuring that mating and ovulation are correctly timed (T/F) ?
True.

Gonadal steroids; (a) influence ovulation, (b) estrous behavior & estrous cycles, & (c) preparation of reproductive tract & mammary gland