Polypeptide Hormones and Puberty Flashcards
What are the two purposes of the menstrual cycle?
- To transport gametes to the site of fertilisation
2. To provide a suitable site for implantation
What is an estrous cycle?
A behavioural strategy to ensure mating at the time of ovulation. Occurs in mammals that dont have a menstrual cycle.
What 3 aspects comprises the estrous cycle?
Attractiveness - the value the female has as sexual stimulation for the male. It has been shown that females secrete a pheromone when they are at their most fertile.
Receptivity - willingness to accept male advances
Proceptivity - behavioural gestures to entice the male
What are the psychosocial factors that can mask a hidden heat period in women?
− development of sexual self-image in childhood − age of sexual debut and sexual history − current sexual self image − lifespan of current relationship − relationship satisfaction − contraceptive use − pregnancy motiviation − past history of terminations − cycle related chance in emotional and physical well being − health level and stress levels − personality type (introvert/extravert)
What is the evidence for a hidden heat period in women?
Proceptivity:
• Women show increased sexual motivation that biases recognition performance towards objects with a sexual meaning
• Sex stimuli rated less often as negative during the periovulatory phase than during menses and luteal phase
• Students judged more masculine male faces as more attractive during the follicular phase
• Women evaluate androstenone (a human unattractive sweat substance with more production in males) as more pleasant during ovulation
• A study has also suggested that women dance more provocatively when at their most fertile!
Receptivity:
• Depending on the phase of the menstrual cycle, the mood of women is affected by smelling of androstenol, which illicits a positive attitude towards males → they rated their moods as more submissive in the middle of the menstrual cycle
• Not much other evidence of more frequent intercourse at the time of ovulation, but it is thought this is masked by the psychosocial factors.
Attractiveness:
• Reported that vagina secretions have a less unpleasant odour around ovulation – but these aren’t really attractive to humans anyway
• Men seem to rate womens body odour as more pleasant around ovulation
Define Puberty
When an immature individual acquires the physical and behavioural attributes which will allow him or her to reproduce.
What controls the timing of puberty?
Genetics:
• Twin studies show that genetic influences are the single largest factor accounting for variation in pubertal development
External factors:
May modulate the timing of puberty present by genetics:
• Stress
• Intra-family relationships
• Endocrine disrupting chemicals
• Adiposity → one of the biggest external regulators
− First clue that adiposity was linked with puberty came at looking how the age at menarche changes over the years
− Age has decreased by 2-3 months per decade between 1840 and 1979
− in developed counties, this decrease has ceased over the last 40 years
− Given rise to the idea that a critical body weight must be met.
What is the role of nutrition in the initiation of puberty?
• Puberty is later in counties with a sub-optimal economic status
• Delayed puberty occurs in association with
− Malnutrition ( anorexia nervosa)
− Elite athletes (gymnasts and ballerinas)
• Moderate obesity associated with advanced puberty
How does the brain know when a critical weight is met?
• Leptin – a signal from white adipose tissue
− Levels increase at the start of puberty
− Leptin k/o mice have low gonadotrophin levels and underdeveloped gonads
− Similar phenotype in humans with mutations in leptin or the receptor
− Abnormalities reversed by leptin therapy
➢ However, the leptin receptor is not expressed by GnRH neurons!
Where is Kisspeptin produced?
− Arcuate nucleus – interesting, as this is almost important for GnRH pulse generation
− Anteroventral periventricular nuclei – sexually dimorphic, more produced in females
• Scattered populations of Kiss1 neurons have also been suggested in the medial amygdyala and preoptic nucleus - populations of uncertain significance
• The fact the AVPV produces more kisspeptin in females has lead to the idea that perhaps the ARC is responsible for negative regulatory effects of steroids, and the AVPV is responsible for positive.
How do the sexual dimorphisms in Kisspeptin production occur?
− In this context, experimental evidence suggests that Kiss1 neurons are more sensitive to the organizing effects of sex steroids acting during critical windows of differentiation
− Thus, exposure of female rats to high levels of testosterone during this period induces the masculinsation of the Kiss1 neuronal population at the AVPV
− Suggests that the increase in testosterone that occurs in males at this stage of development (between late gestation and early neonatal) is responsible for the virtual absence of kiss! neurons in this rostral area.
− Early withdrawal of testosterone by neonatal gonadectomy of males apparently feminizes the population of Kiss1 neurons at the AVPV, and makes them capable of responding to the positive feedback of estradiol.
How does Kisspeptin function at its receptor?
Kisspeptin acts at a GPCR – GPR54.
GPR54 is expressed by GnRH neurons
GPR54 signals through Gαq
Receptor is activated
G alpha subunit dissociates from the g beta-gamma subunit, and activates Phospholipiase C
This hydrolyses PIP2 (located at the inner leaflet of the plasma membrane) to produce DAG
DAG activates PKC which goes on to activate the downstream effectors to cause GnRH gene transcription
Is kisspeptin regulated by leptin?
• Reproduction is a metabolic demanding function that requires suffient levels of energy stores to proceed
• GnRH secretion is influenced by a number of metabolic signals, such as glucose, leptin, insulin and ghrelin. These may not necessarily operate directly on GnRH neurons – an example of this being leptin.
• Several studies have documented a clear impact of conditions of undernutrition or metabolic stress on Kiss1 expression – thus mice subjected to fasting display a significant reduction in hypothalamic Kiss1 mRNA.
• Given the important permissive role of leptin in the metabolic control of puberty onset, its role as a putative regulator of hypothalamic Kiss1 has been evaluated in different species.
− Low leptin levels are associated with reduced hypothalamic expression of Kiss1
− Administration of leptin enhances Kiss1 mRNA levels
− This suggests that leptin acts on kisspeptin neurons through leptin receptors.
However! This has recently been challenged by Donato et al:
• Mice with genetic deletion of Leptin R specifically from Kiss-1 expressing cells did not show alterations in puberty onset
• However, in this model, the mouse congenitally lacks LepR, so a developmental compensatory mechanisms may have taken place
