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Reproduction > Neuroendocrine and feedback mechanisms in Reproduction > Flashcards

Neuroendocrine and feedback mechanisms in Reproduction Flashcards

1
Q

What are the three main ways that the hypothalamus interacts with the pituitary gland?

A
  • Hypothalamic inputs
  • Feedback effects of circulating hormones
  • Paracrine and autocrine secretions of the pituitary
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2
Q

What is hypothalamic control of the pituitary gland?

A

A system that underlies the ability of mammals to coordinate endocrine functions that are necessary for survival.

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3
Q

What is gonadotropin-releasing hormone (GnRH)?

A

A hypothalamic hormone that controls the release of luteinizing hormone and follicle-stimulating hormone from the pituitary.

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4
Q

Where is GnRH released from?

A

arcuate and the preoptic nuclei of the hypothalamus

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5
Q

How are LH and FSH released?

A

Stimulated by GnRH through the hypophyseal portal system. Released from the anterior pituitary gonadotrophs.

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6
Q

What are the two types of GnRH secretion?

A

Pulsatile , Episodic

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7
Q

What is pulsatile GnRH secretion?

A

Governs the release of the pituitary gonadotrophins.

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8
Q

What factors can influence GnRH secretion?

A

Stress, exercise and diet

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9
Q

When is GnRH first detectable?

A

10 weeks gestational age

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10
Q

When are FSH and LH first produced?

A

10-13 weeks gestational age

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11
Q

Compare the levels of GnRH from Birth to Adulthood.

A

BIRTH-6 MONTHS: elevated levels of GnRH, then subsequent decrease for the remainder of childhood

Pre-puberty: infrequent, small pulses of GnRH; LH and FSH secreted in very small amounts.

Puberty: Sharp increase in amplitude and frequency of pulses of GnRH

Adult: HPG axis activated continues to function in men and becomes deregulated in women (leads to menopause)

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12
Q

Which factors contribute to the GnRH pulsatility ?

A
  • Several hormonal and neural pathways that convey different types of regulatory information.
  • Morphological changes in the GnRH neurons: Spontaneous auto-rhythmicity, functioning as an intrinsic mechanism to secrete GnRH in a pulsatile manner.

-Inhibitory as well as excitatory afferent signals from distinct neurotransmitters Noradrenergic, dopaminergic, serotoninergic, and opioidergic pathways; inhibitory neurotransmitters (GABA); excitatory amino acids (glutamic acid, aspartic acid).

  • The kisspeptin-neurokinin b-dynorphin (kndy) neuronal network: Synergic action to induce coordinated and pulsatile GnRH secretion by regulating the neuroactivity of other KDNy cells.
  • Steroids Negative Feedback
  • Nutrition and metabolism: Adequate leptin level (peptide primarily produced by white adipose tissue) permits the activation of the GnRH pulse generator
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13
Q

What are gonadotropins?

A

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act on the ovaries and testes to direct gametogenesis and sex steroid hormone synthesis.

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14
Q

What does LH do in males?

A
  • stimulates Leydig cells to produce testosterone
  • Induces and maintains spermatogenesis and secondary sexual characteristics
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15
Q

What does FSH do in males?

A

stimulates spermatogenesis (sperm production)

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16
Q

How is the synthesis and secretion of LH and FSH regulated?

A
  • Hypothalamic input
  • Positive and negative feedback from gondal sex steroid and peptide hormones
  • Paracrine modulation from local factors produced within the pituitary gland
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17
Q

What frequency of pulsative GnRH favours LH?

A

Rapid GnRH pulse frequencies

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18
Q

What frequency of pulsative GnRH favours FSH?

A
  • Slower pulse frequencies
19
Q

What are inhibins?

A
  • Circulating endocrine hormones, that originate in the gonads and act on the pituitary , specifically inhibiting the FSH Beta subunit
20
Q

What are activins?

A

-Potent stimulatory effects on FSH expression
Produced in gonads and pituitary glands

21
Q

What is follistatin?

A
  • A protein that binds activin and prevents activin binding to the activin receptor.
  • Potent inhibitor of FSHB expression and secretion
22
Q

How do gonadal steroids control goandotropins?

A
  • Regulate GnRHR expression and signalling
  • Directly regulate the production of gonadotropins
23
Q

What two steroid hormones exert negative feedback effects on gonadotropin secretion in males?

A

Testosterone and oestradiol.

24
Q

How does Testosterone inhibit GnRH secretion?

A

Feeds back on the hypothalamus.

25
Q

How does testosterone inhibit LH secretion?

A

Feeds back at the level of the pituitary.

26
Q

What stimulates spermatogenesis?

A

FSH acts indirectly on Sertoli cells. Testosterone stimulates the final stages of spermatogenesis.
- Sertoli cells release inhibin , which inhibits further release of FSH from the pituitary.

27
Q

What is the ovary responsible for?

A
  • periodic release of oocytes and production of steroid hormones
  • integrated into cyclic process of follicular maturation, ovulation, and formation and regression of the corpus luteum.
28
Q

What does the ovarian cycle do?

A

governs the preparation of endocrine tissues and release of eggs.

29
Q

What does the menstrual cycle do?

A

Prepares and maintains the uterine lining

30
Q

What is the average length of the ovarian and menstural cycle?

A
  • 22-32 day cycle
  • Average 28 days
31
Q

What is the most important role of the HPG axis in female reproduction?

A

To control the uterine (menstrual) and ovarian cycles.

32
Q

What are the phases in the menstrual cycle?

A

follicular phase, ovulation, luteal phase, menstruation

33
Q

What is the follicular phase?

A
  • FSH and LH cause the growth of follicles on the surface of the ovary
  • LH acting on the Theca cells induce the secretion of androstenedione.
  • This is converted to oestradiol by aromatase secreted from the granulosa cell after FSH stimulation.
  • As the follicles grow, more oestrogens are released, which will inhibit the secretion of LH and FSH at hypothalamus.
  • Stimulation of only ONE follice.
34
Q

What is the process of ovulation?

A
  • Day 14 of the menstrual cycle , due to oestrogen induced LH surge.

-2 days before ovulation, the granulosa cells begin to develop LH receptors, as well as FSH. The dominant follicle keeps secreting more oestrogens.
- The rising oestrogen levels make the pituitary gland more responsive to the GnRH
- Oestrogens become a positive feedback signal , triggering the mid cycle ovulatory surge of LH and FSH secretion.

  • The increased LH and FSH , acting on the granulosa and theca cells facilitate the rupture of the follicle and the release of oocytes.
35
Q

What is the luteal phase?

A
  • period of corpus luteum activity (days 14-28)
  • LH levels are still high and the remaining follicles turns into Corpus Luteum.
  • Luteinized theca cells respond to the low concentration of LH by producing Progesterone.
  • Luteinised granulosa cells secret inhibin which inhibits the secretion of FSH from pituitary gland.
  • Oestrogen levels decrease and progesterone levels increase.
  • Progesterone makes the endometrium receptive to the implantation of fertilised gamete and as negative feedback on the pituitary gland.
  • If the implantation does not happen, corpus luteum replaced corpus Albicans, no hormones produced, spiral arteries collapse = Menstruation.
36
Q

What are some defects of GnRH and GnRH receptors?

A

Defects in the process of synthesis, release and action of GnRH.

37
Q

What is hypogonadotropic hypogonadism?

A

deficient sex steroid production due to decreased gonadotropin secretion

38
Q

What is Kallmann syndrome?

A

Hypogonadotropic hypogonadism due to a lack of gonadotropin-releasing hormone (GnrH) due to failure of
migration of the GnrH neuron from the olfactory bulb. These patients are anosmic and have primary amenorrhea.

39
Q

What are the effects of gonadotropin deficiency?

A

Hypogonadism with decreased sex steroid production.

40
Q

what is a GnRH agonist ?

A
  • An analogue that activates the GnRH receptor resulting an increased secretion of FSH and LH.
41
Q

What happens when there is prolonged activation of GnRH receptors by GnRH agonists?

A
  • Leads to desensitization and down regulation of GnRH receptors. Supresses gonadotrophin.
42
Q

What are GnRH agonists used for in females/ males?

A
  • Female infertility to initiate an LH surge and ovulation
  • Uterine fibroids
  • Controlled Ovarian Hyperstimulation to supress endogenous LH surge and to prevent premature ovulation
  • Male Infertility due to hypothalamic hypogonadotropic hypogonadism.
  • Diagnosis of LH responsiveness in differentiating delayed puberty
  • Controlled ovarian hyperstimulation to supress endogenous LH surge and to prevent premature ovulation.
    Central Precocious puberty.
43
Q

What is a GnRH antagonist?

A

An analogue that blocks the GnRH receptor, resulting in an immediate drop in FSH, LH secretion.

Men: Leads to a rapid suppression of testosterone release from the testes.

Women: Leads to suppression of oestrogen release from the ovaries.

44
Q

What are GnRH antagonists used for?

A

Prevention of premature LH surge and ovulation for in vitro fertilization, advanced prostate cancer to reduce gonadotropins and androgens more rapidly than GnRH agonists. Avoids testosterone surge seen with GnRH agonist therapy.

Reproduction (22 decks)

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