Hormonal regulation of reproductive function and estrus cycle

Question 1

Reproduction is regulated by an interplay of: (2)

The nervous system translates external stimuli into neural signals in two different ways:

Answer 1

• The nervous system
• The endocrine system

The nervous system translates external stimuli into neural signals in two different ways:
1. A simple neural reflex
2. A neuroendocrine reflex

Who is involved in this: sensory neurons, the spinal cord, efferent neurons, target tissue.

Question 2

Regulation of reproduction:
Describe the simple neural reflex.

Answer 2

stimulus to sensory neurons,
transmission of signal to efferent neurons via spinal cord or interneurons

neurotransmitter is released,
that targets target tissues,
target tissues respond.

Question 3

Regulation of reproduction:
Describe the neuroendocrine reflex.

Answer 3

stimulus to sensory neurons,
transmission of signal to efferent neurons via spinal cord or interneurons.

hypothalamus is stimulated,
neurohormone is released into blood,
travels to target tissue,
target tissue responds.

Question 4

The hypothalamus (3) and the pituitary (2) are made up of what parts?

Answer 4

Hypothalamic nuclei, clusters of nerve cell bodies ex:
* Tonic center
* Surge center (only in females)
* Paraventricular nucleus (PVN)

The pituitary:
* The anterior lobe / hypophysis
* The posterior lobe / neurohypophysis

Question 5

Decribe how the hypothalamo-hypophyseal-portal system works.

Answer 5

The hypothalamic neurons release neuropeptides (gonadotropin releasing hormone, GNRH) →

they enter the capillary system at the stalk of the pituitary →

are deposited in the capillary plexus →

act directly on the cells in the anterior lobe.

Question 6

The paraventricular nucleus and the posterior lobe of the pituitary dose not have a

Answer 6

Does not have a portal system, instead it has long neurons that reach into the posterior pituitary / neurohypophysis.
Direct stimulation releases neurohormone into a blood plexus in the posterior lobe.

Question 7

Hypothalamic hormones (neuropeptides): (6)

Answer 7

thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH),

growth hormone-releasing hormone (GHRH),
corticotropin-releasing hormone (CRH),

somatostatin, and
dopamine

Question 8

Pituitary hormones (gonadotropins): are released into the blood from

Answer 8

the anterior hypophysis mostly, e.g.
follicle simulating hormone(FSH),
luteinizing hormone (LH) and
prolactin but from the posterior lobe, oxytocin.

Question 9

Gonadal hormones (sex steroids): originate from the gonads and affect the function
of (3)

Answer 9

the hypothalamus,
the anterior lobe of the pituitary and the tissues of the reproductive tract.

Question 10

The ovaries produce what hormones? (6)

Answer 10

estrogens,
progesterone,

inhibin,
some testosterone,

oxytocin
and relaxin.

Question 11

The testes produce what hormones: (6)

Answer 11

testosterone and other androgens,

inhibin/activin,

anti-mullerian hormone(AMH) and estrogen.

Question 12

Uterus produces what hormone:

Answer 12

prostaglandin PGF2

Question 13

Placenta produces what hormones: (3)

Answer 13

progesterone, estrogen, relaxin

Question 14

The overall fundamental mechanisms controlling the secretion of reproductive
hormones and the reproductive functions are the:

Answer 14

Positive and negative feedback mechanisms.

1. Negative feedback = suppression of GnRH neurons

progesterone increases in e.g. pregnancy→
GnRH decreases →
FSH/LH decrease →
resulting in little follicular development and the female will not cycle during pregnancy.

2. Positive feedback = stimulation of GnRH neurons

estrogen increases →
GnRH increases →
FSH/LH increase →
resulting in stimulation of follicular growth and ovulation.

Question 15

Estrus cycle consists of the physiologic events that happens between 2
ovulations. (2)

Answer 15

Follicular phase made up of:
proestrus and estrus, dominated by estradiol, growth of the dominant follicles

Luteal phase made up of:
metestrus and diestrus, dominated by progesterone

Anestrus is just the cessation of estrus cycles, insufficient GnRH release.

Question 16

Follicular phase made up of:

Answer 16

proestrus and estrus

dominated by estradiol, growth of the dominant follicles

Question 17

Luteal phase made up of:

Answer 17

metestrus and diestrus

dominated by progesterone

Question 18

Estrus cycles are categorized after the frequency of occurrence through the year: (3)

Answer 18

• Monoestrus: having 1-2 estrus cycles/year and a defined anestrus between (bitch)
• Seasonally polyestrus: several estrus cycles, that occur during a certain time of the year (cat, ferrets, horse)
• Polyestrus: uniform distribution of estrus cycles throughout the year (ruminants, rodents)

Question 19

Describe the Estrus cycle of the bitch.

Answer 19

Its a little different in dogs compared to other animals.

Consists of: proestrus, estrus, diestrus and a long anestrus.

The bitch is a monoestral nonseasonal spontaneous ovulator.

Most bitches have 3 estrus cycles in 2 years but some bitches have up to 4
periods/year, varying between breeds.

Question 20

Why can we measure progesterone in dogs to estimate ovulation time?

Answer 20

The CL begins to form (prelutenization) in dogs before actual ovulation occurs.

Question 21

In the bitch - how long do proestrus and estrus last?
And diestrus?

Answer 21

pro 7-10 days
est 7-10 days
diestrus after ovulation, 2 months

Question 22

Describe Proestrus in bitches.

Answer 22

• Increasing GnRH from hypothalamus results in
• Excretion of FSH and LH from the anterior part of the pituitary and stimulation
  of the ovaries which results in
• growth of the follicles and increase the production of estradiol from the granulosa cells in the follicle wall
• As follicles mature they produce inhibin, that inhibits FSH in late proestrus
• Follicular estrogen promotes increased vascularity and edema of the reproductive tract and activity of the glandular epithelium
• In the uterus the mucosal capillaries leak resulting in plasma cells and blood to
  the lumen (diapedesis) resulting in serosanguinous vulvar discharge in bitches in heat.

Question 23

What produces inhibin and what is its function?

Answer 23

As follicles mature they produce inhibin, that inhibits FSH in late proestrus.

Question 24

What causes bitches to bleed during heat?

Answer 24

Follicular estrogen promotes increased vascularity and edema of the reproductive tract and activity of the glandular epithelium

In the uterus the mucosal capillaries leak resulting in plasma cells and blood to
the lumen (diapedesis) resulting in serosanguinous vulvar discharge in bitches in heat.

Question 25

Describe estrus in bitches.

Answer 25

Elevated concentrations of estrogens, which decline prior to ovulation.

When estrogen reaches it’s threshold, the LH-peak appears, due to a surge in GnRH (surge center), 48-60 hours before ovulation.

 For ovulation to occur a decline in estrogen and a rise in progesterone
is required.

 Preovulatory luteinization of the follicle wall occurs prior to ovulation with an increase in progesterone.

 The decline in estrogen and increase in progesterone appears to stimulate the LH-surge as well as being responsible for the change in sexual behavior.

Question 26

For ovulation to occur in the bitch, a decline in what hormone ?and a rise in what hormone? is required.

Answer 26

a decline in estrogen and a rise in progesterone is required.

Question 27

Describe ovulation in the bitch.

Answer 27

Very large variations in relation to the day on which the ovulation occurs after onset of proestrus (average 12 days, but it can appear as early as day 5 or as late as day 30).

Oocytes are immature at the time of ovulation →
Fertilization appears after extrusion of the first polar body and completion of the first meiotic division, to form the secondary oocyte.

The maturation takes about 48-60 hours → optimal time of mating is approx. 2 days after ovulation?

Question 28

Maturation of the oocyte in the bitch occurs

Answer 28

about 48-60 hours after ovulation

Fertilization appears after extrusion of the first polar body and completion of the first meiotic division, to form the secondary oocyte.

Question 29

Describe diestrus in the bitch.

Answer 29

begins approximately 7-9 days after the LH surge

Corpus luteae are functional, progesterone concentrations continue to increase.

The rise in progesterone begins during the preovulatory LH surge and continues
to increase to mid-diestrus.

Progesterone cause mucosal secretions, decreases smooth muscle excitability, closes the cervix and prepares the uterine environment for the support of an embryo.

Question 30

Describe Reproduction in ferrets.

Answer 30

The ferret comes into puberty at 8-12 months.

The female is a poly-estrus seasonal breeder. Induced ovulator.

❖ Proestrus in january- february for 2-3 weeks, then persistent estrus from march- september → persistent vulvar swelling if ovulation is not induced.

The matings are long lasting (1-3 hours) and violent.

Question 31

Ferret pregnancy length is

Answer 31

40-44 days

If the female is mated → ovulation happens → but if no pregnancy occurs → pseudopregnancy occurs for 40-42 days → estrogen levels decline.

The average litter size is 8 pups born deaf and blind. The weaning period is 6-8 weeks.

Question 32

Well known problems in the ferret (3)

Answer 32

Estrogen intoxication due to persistent estrus without ovulation → Ovulation is induced by breeding, if no breeding → persistent estrus with persistent estrogen production leading to
→ hyperestrogenism
→ bone marrow suppression
→ pancytopenia.

❖ Ovarian remnant syndrome

❖ Hyperadrenocorticism

Question 33

Clinical symptoms of estrogen intoxication in ferrets. (8)

Answer 33

 Swollen vulva
 Bilateral alopecia

 Anorexia
 Pale mucosal membrane (non-regenerative anemia)

 Melena
 Petecchiae and ecchymoses (thrombocytopenia)

 Abdominal enlargement
 Secondary bacterial infections (neutropenia)
→ DEATH

Question 34

How to prevent persistent estrus and estrus toxicity in ferrets. (3)

Answer 34

Induce ovulation, by using a vasectomized male → pseudopregnancy→
decrease in estrogen.

Medicate with Proligestone (progestin) in the beginning of estrus → pseudopregnancy (risk of pyometra).

Implant GNRH analog deslorelin implant (Suprelorin®)

Question 35

Tx of estrogen toxicity in ferrets. (2)

Answer 35

It’s a question of decreasing the bone marrow suppression:

1. Ovariohysterectomy → surgical/ anestesia risk and increased risk of
   hyperadrenocorticism.
2. Induce ovulation with → hCG 100IU/kg IM (can be repeated in 1-2 weeks)

Question 36

Ferrets are at high risk of developing hyperadrenocorticism. Why?

Answer 36

Often seen in neutered female ferrets
→ increase in GNRH after neutering
→ Persistent stimulation of adrenal cortex
→ Hyperplasia and tumor formation in the adrenal gland (nodular hyperplasia,
adenoma adenocarcinoma)
→ Increase in androstenedione, estradiol and 17-hydroxyprogesterone

Result is hyperadrenocorticism and hyperestrogenism secondary to adrenal gland disease.

Symptoms:
❖ Vulvar swelling (neutered females)
❖ Return of sexual behavior
❖ Symmetrical alopecia

Treatment:
❖ Surgery
❖ GNRH implant (suprelorin®)