End of lecture 10 - hypothalamic Flashcards
Hypothalamus
- important for reproductive function
- secretes GnRH
- GnRH is released in pulses which is crucial for the functioning of the HPGA.
- GnRH pulsatility rhythm can alter (suppress or increase) the release of gonadotrophin (LH and FSH) from the pituitary.
Hypothalamic-Pituitary-Gonadal Axis (HPGA)
GnRH stimulates the production and release of two gonadotrophin from the anterior pituitary:
1. Follicle-Stimulating hormone (FSH)
2. Luteinising hormone (LH)
FSH and LH stimulate the gonads (in males the testes and females the ovaries)
Ovaries - FSH
FSH: stimulates the development of ovarian follicles (egg) for ovulation (produces estrogen)
- estrogen stimulates proliferation of the endometrium
Ovaries - LH
LH: triggers ovulation and the formation of the corpus luteum (produces progesterone for menstrual cycling and maintains endometrium)
If no conception occurs, endometrium is shed during menstruation
Testes - FSH
- together with testosterone, stimulate sperm production
- sperm production: steroli cells
Testes - LH
- stimulates production and release of testosterone
- testosterone: leydig cells
What causes the maturation of the HPGA axis during puberty? (2 hypothesis)
Gonadostat hypothesis: pre-puberty the GnRH pulse generator is highly sensitive to gonadotrophin levels (LH and FSH). During puberty, the sensitivity decreases, resulting in an increase in gonadal steroids (estrogen and testosterone)
Hypophysiotropic Hypothesis: Puberty is associated with an increase in positive feedback by stimulatory factors (neurotransmitters). These factors enhance the activity of the GnRH pulse generator, promoting its release.
Correlates of HPGA maturation
- somatotropic axis
- adrenarche
- insulin sensitivity
- body composition
- skeletal maturation
Somatotrophic (GROWTH) axis
Hypothalamic Regulation: The hypothalamus releases two key hormones:
1. Growth Hormone-Releasing Hormone (GHRH): Stimulates the anterior pituitary to secrete GH.
2. Somatostatin (SS): Inhibits GH release.
Pituitary Gland Action: The anterior pituitary responds to GHRH by increasing GH secretion, while somatostatin suppresses it (keeping it balanced).
Role of Growth Hormone (GH): GH, once in the bloodstream, stimulates the liver and other tissues to produce IGFs, particularly IGF-1.
Effects of GH and IGF-1: Together, they promote skeletal growth (increasing height) and enhance protein synthesis (muscle growth and repair).
Adrenarche
Adrenarche is a significant developmental stage that occurs during childhood, typically between the ages of 6 and 10, and marks the onset of increased adrenal hormone production
- During adrenarche, the adrenal cortex develops a third layer (zona reticular) and begins producing large amounts of adrenal androgens, DHEA and androstenedione that can produce testosterone and estrogen
- Rise in DHEA and androstenedione levels occurs before any detectable increases in gonadotropins (LH and FSH) and gonadal steroids (estrogen and testosterone). This means that the adrenal glands start producing these androgens independently of the changes occurring in the gonads, marking a significant developmental milestone.
- associated with the early development of secondary sexual characteristics, such as pubic and axillary hair growth, and may influence mood and behavior during this transitional phase.
- so it has been suggested that these weak androgens may contribute to the maturation of the HPGA
Insulin and its role on growth
- insulin and growth hormone (GH) up-regulate each other
- elevated insulin leads to increased levels of IGF-1 (IGF-1 and GH induces height and muscle growth)
Insulin sensitivity and HPG axis maturation
- elevated insulin levels lead to increases in gonadal steroid hormone levels
- during puberty there is a transient decrease in insulin sensitivity –> “insulin resistance” –> increase in insulin levels –> increases in gonadal steroid –> puberty development
- hypo-insulinemic states (Type 1 diabetes) –> delayed pubertal development
Body composition
- 1978, Frisch proposed the “fatness threshold” hypothesis, suggesting that a certain level of body fat (approx 17%) is necessary for the onset of menarche (the first menstrual period) in girls. They argued that this threshold is critical for the activation of the HPGA, which regulates reproductive hormones.
Criticism: argue that the relationship between body fat and the onset of puberty is not as straightforward as proposed due to genetics, environmental influences, and overall health also play significant roles in the timing of puberty.
- many see the increased in fat mass as a consequence of HPGA maturation and not as its cause
- Ellison, 1981, the onset of puberty actually correlates with skeletal dimensions, not % body fat
Skeletal Maturation
- striking synchronisation of reproductive and skeletal maturation in humans
- high correlation between menarche and attainment of adult pelvic size
Skeletal maturation hypothesis: timing of puberty is coordinated with the attainment of appropriate physical size for reproduction
Why would the HPGA be so sensitive to the rhythm with which the hypothalamus releases GnRH pulses?
Because it allows our organisms to:
- adjust reproductive maturation and, then, function to the quality of the environment
- as long as development is not complete, reproduction necessarily comes second to growth and always second to surviving
