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MBB6345 Reproduction and fertility > The HPG axis > Flashcards

The HPG axis Flashcards

1
Q

What is HPG?

A

The hypothalamic-pituitary-gonadal axis

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2
Q

What is the HPG axis part of?

A

The endocrine system

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3
Q

What do endocrine glands do?

A

Endocrine glands secrete hormones into the bloodstream; the hormones travel to and act on other organs or tissues

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4
Q

Describe the axis? And what does this include?

A

Axis: multiple endocrine glands working together as a system to regulate development, reproduction, and aging in animals.

Hypothalamus
Anterior pituitary
Testes/ovaries

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5
Q

Describe the position hypothalamus

A

Component of forebrain; part of the diencephalon

Hypothalamus is in contact with the anterior pituitary gland

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6
Q

Function of the hypothalamus

A

Regulates many core body functions (homeostatic functions) eg. Metabolism, growth, reproduction, stress.

Secretes a peptide hormone: gonadotrophin releasing hormone (GnRH; 10aa long)

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7
Q

What is the pituitary glad composed of?

A

Posterior and anterior; derived from separate types of cells during embryogenesis; different functions.

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8
Q

Describe the anterior pituitary gland

A

Anterior pituitary is an endocrine gland.

Made up of different groups of cells:
Thyrotropes (Thyroid-stimulating hormone; TSH)
Somatotropes (Growth hormones)
Gonadotrophs (Follicle-stimulating hormone; FSH and Luteinising hormone; LH)
Corticotropes (adrenocorticotropic hormone; ACTH)
Lactotropes (prolactin; PRL)

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9
Q

Where does GnRH travel?

A

GnRH from the hypothalamus travels in the portal blood to the anterior pituitary where it acts on gonadotrophs

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10
Q

What does GnRH binding result in?

A

GnRH binding results in a signalling cascade culminating in expression of luteinising hormone (LH) and follicle-stimulating hormone (FSH), both heterodimeric glycoprotein hormones

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11
Q

What do Gonadotroph cells release?

A

Gonadotrophs release LH and FSH for transport to the ovaries and testes via the bloodstream

Gonadotrophs are specialized cell types of the anterior pituitary that synthesize and secrete LH and FSH.

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12
Q

What does GnRH stimulate?

A

GnRH stimulates gonadotrophin proliferation and hormone production via GnRHr receptor

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13
Q

The HPG axis

A

Diagram…

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14
Q

What are the three main sex steriods? Give examples…

A

Three main types of sex steroid: Progestagens (e.g. progesterone),

Androgens (e.g. testosterone; dihydrotestosterone; androstenedione)

Oestrogens (e.g. oestradiol; oestrone)

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15
Q

Descrobe sex steriods

A

All derived from a common precursor: cholesterol

Interconversion occurs via a biosynthetic network; enzymatic defects at a single point in the network can have far-reaching effects

Action of these steroids is dictated by tissue-specific receptors

Once inside a cell, steroid-receptor complexes bind to steroid response elements on DNA and impact on transcription

The sex steroids are essential for normal reproductive development, gametogenesis and the maintenance of secondary-sex characteristics

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16
Q

How do the three sex steriods play a major role?

A

Progesterone (P), Testosterone (T) and Oestrogen (E) play major feedback roles via action on pituitary gonadotrophs

17
Q

What to the sex steriods do once theyve entered a gonadotroph

What does this regulate?

A

The hormones enter the cell and combine with their receptors. Hormone-receptor complexes translocate to the nucleus and mediate negative transcriptional control of the target genes

This regulates the production of FSH, LH and also the GnRH receptor, thus reducing gonadotroph stimulation from the hypothalamus

18
Q

What do male and female gonadal cells express? Describe cascade of events

A

Male and female gonadal cells also express Inhibin and Activin, members of the transforming growth-factor-β (TGF-β)) family

They bind to Inhibin and Activin receptors on the gonadotroph cell

They exert opposing actions on FSH expression. Inhibin also binds to Activin to modulate its activity

Both protein families have other diverse biological roles e.g. germ cell development; tumour suppression; erythropoiesis

19
Q

WHat is GnRH essential for?

A

GnRH is essential for gonadal function: destruction of GnRH neurons, generation of genetically null GnRH mice, or immunisation against the GnRH peptide all result in gonadal atrophy

20
Q

GnRH release

A

GnRH release is pulsatile (~1 per hour). GnRH pulses begin at puberty. Pulse generator resides in hypothalamus

21
Q

How are anterior pituitary hormones released?

A

Anterior pituitary hormones are also released in a pulsatile manner in post-pubertal humans. Very little is released before puberty

22
Q

How can alterations in the output of LH and FSH be achieved?

A

Alterations in the output of LH and FSH can be achieved by:

Increasing or decreasing the amplitude or frequency of GnRH pulses

Modulating the response of the gonadotrophs to the pulses

23
Q

How is GnRH secretion regulated?

What is RFRP-3?

A

Kisspeptin: master player of control of reproduction; 54 amino acid neuropeptide (encoded by KISS1)

It binds to the GPR54 receptor (or KISS1R) found in GnRH neurons; Kisspeptin is a potent GnRH stimulator

KISS-1 +ve neurons are direct targets of oestrogens. Binding of oestrogen results in negative feedback by decreasing GnRH expression

RFamide-related peptide 3 (RFRP-3) is a mammalian orthologue of Gonadotropin-inhibitory hormone (GnIH).

It acts on the gonadotrophs, kISS-1 neurons and GnRH neurons in the hypothalamus. It results in reduced GnRH output and also suppresses the signalling cascade within gonadotrophs that are responsible for LH and FSH expression

24
Q

Whats the potential function of kisspeptin neurons

A

Mediating the relationship between enegry balance and reproduction

25
Q

WHere are kisspeptin neurons?

A

Kisspeptin neurons in the arcuate nucleus (ARC) of the hypothalamus

26
Q

How do they control reproduction?

A

Control reproduction through stimulation (+) of gonadotropin-releasing hormone (GnRH) neurons to regulate gonadal sex steroid production, which then has an inhibitory effect (−) on kisspeptin neurons.

Kisspeptin neurons are also regulated by changes in energy balance. Levels of circulating metabolic hormones such as leptin, insulin and ghrelin are relayed onto kisspeptin neurons. Kisspeptin neurons also regulate energy expenditure and adipose tissue levels although the mechanisms underlying these observations are unknown.

27
Q

How are kisspeptin neurons also regulated?

A

Kisspeptin neurons are also regulated by changes in energy balance.

Levels of circulating metabolic hormones such as leptin, insulin and ghrelin are relayed onto kisspeptin neurons.

28
Q

What do kisspeptin neurons also regulate?

A

Kisspeptin neurons also regulate energy expenditure and adipose tissue levels although the mechanisms underlying these observations are unknown.

29
Q

Control of puberty onset

A

Puberty is metabolically gated; many peripheral hormones and central transmitters involved in sensing metabolic state (e.g. insulin, leptin, ghrelin)

30
Q

Leptins role in puberty

A

Leptin is necessary for puberty to proceed, but is not the sole requirement. Leptin acts on GnRH neurons indirectly (via other neurons, including Kiss1-neurons). Correlation between levels of fat and leptin

31
Q

What happens at puberty with kisspeptin-GnRH axis?

A

At puberty, the kisspeptin-GnRH axis becomes fully activated. A pulse generator mechanism results in regular production of kisspeptin and the cyclical release of GnRH from the GnRH-neurons

32
Q

Self assessment questions

A

What are the commonalities between the HPG axis in males and females?

What are the key positive and negative feedback loops in the HPG axis?

What happens to stimulate the HPG axis at puberty?

MBB6345 Reproduction and fertility (14 decks)

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