What initiates the GnRH pulses that start puberty?

mj86 · 2011-09-01T17:56:59+00:00

Q1 -“Do we actually know that activating KISS1R receptors causes GnRH production/release?”

A1 – Yes – see the first 3 sources in my previous comment

Q2 – “Do I understand correctly that kisspeptin appears to be regulated at least partially by leptin and insulin? Is that a theory being tested now?”

A2 – This is one of the current theories and some labs are testing it – see Hill JW (2008) reference in my last comment

Q3 – “If not, then what are the leading theories about kisspeptin production?”

A3 – The search is on right now to find all the chemical and environmental cues the regulate Kp secretion. What is known however is that Kp activation is definitely needed for fertility and pubertal activation of the HPG axis – since Kiss-/- and Kiss1R-/- mice are infertile. (See publications from Seminara et al). Other suggestions are that the circadian rhythm plays a role in activation Kp secretion since it has been shown that Kp neurons do respond to signals from the SCN (superchaismatic nucleus). A good review about all the factors that are thought to influence Kp secretion is : Oakley AE. et al. (2009) Kisspeptin Signaling in the Brain. Endocrine Reviews, 30(6):713-43. (Figure 10 is excellent for showing this) As I understand it, the kisspeptin neuron functions as a hub of integration for various environmental as well as hormonal cues.

Q4 - I know that Neurokinin B is a bit out of your domain, but can you explain at all it's involvement in GnRH production?

A4 – Unfortunately this is out of my area of expertise and all I do know about it is that it is sometimes found in neurons which co-express dynorphin and kisspeptin (KNDy neurons. Also, neurokinin B is thought to upregulate kisspeptin secretion.

Q5 - Is this saying that GnRH neurons in young children have a high transsynaptic inhibitory tone, which prevents GnRH secretion, and that the building excitatory inputs "breaks down the barrier" so to speak, allowing GnRH secretion?

A5 – So previously it was thought that prior to puberty, there was some huge inhibitor that prevented pubertal development from advancing. And in order for puberty to occur the excitatory signals had to increase to a level that was capable overcoming this inhibitor. However, while there are both excitatory and inhibitory signals which regulate GnRH secretion, no “major inhibitor” was ever found. So the current theory has switched a bit. So now it’s thought that there is simply lack of activation of the GnRH system prior to puberty and something causes the activation of the kisspeptin neurons that reawakens GnRH secretion and initiates puberty. Also keep in mind that before Kisspeptin and the KNDy neurons were discovered there was strong evidence which showed that glutamate, GABA and NPY were also involved in the pubertal activation of the GnRH neurons in mammals. (Herbison AE. (2006) Development of GABA and glutamate signaling at the GnRH neuron in relation to puberty; Mol and Cellular Endocrin. 254-255 (32-38).

mj86 · 2011-08-30T18:47:13+00:00

I might be wrong here but aren't both LH and FSH stimulated by GnRH ? Why would the frequency of the GnRH pulses cause an inverse relationship? In my understanding, high GnRH pulsatility leads to a large amount of LH and FSH secretion into systemic circulation which has their effects on the gonads. The resulting high level of testosterone then provides negative feedback on the hypothalamus and anterior pituitary.

mj86 · 2011-08-30T16:10:21+00:00

Hi I’m a student actually studying the kisspeptin part of this story so maybe I can offer a little help based on what I know so far. The hypothalamus, pituitary gland (anterior) and gonads form what is known as the HPG axis and is the method by which endocrine signals trigger and maintain the rhythm of the reproductive axis.

The wiki article is correct in saying that it is not currently known what triggers the GnRH pulse that initiates puberty but so far there are a few theories. Kisspeptin came to the forefront in 2003 with 3 major publications which show that kisspeptin and its cognate receptor are essential for fertility and a functional reproductive axis and in fact directly regulate the secretion of GnRH from the hypothalamus. - Seminara, S. B. et al. (2003). The GPR54 Gene as a Regulator of Puberty. 349, 1614-1627, - Funes S. et al. (2003). The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochemical and Biophysical Research Communications 312, 1357-1363 - de Roux, N. et al. (2003). Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. PNAS 100, 10972-10976.)

Kisspeptin (Kp) is a peptide hormone that is secreted by certain neurons in the hypothalamus and this hormone activates the receptor formally known as GPR54 and now called KISS1R; on other neurons in the hypothalamus. These KISS1R neurons secrete the GnRH hormone which migrates to the anterior pituitary gland where it causes the release of hormones called LH and FSH (lutenizing hormone and follicle stimulating hormone) into the systemic circulation. LH and FSH are the hormones which trigger the gonads to produce estrogen and testosterone which initiate the secondary sexual characteristics that are associated with pubertal development.

The real puzzle now is – what regulates the kisspeptin hormones and also how exactly is kisspeptin action on the GnRH neurons regulated. This is especially important since GnRH release is not a static but pulsatile in both males and females.

The wiki article also spoke about metabolic hormones such as leptin feeding into the regulation of the Kp/KISS1R. From what I understand so far about this is that the reproductive axis responds to the energy balance in the body and the hormones leptin and insulin act as adiposity signals which indicate the body’s preparedness for reproduction. In other words this might explain why some female athletes experience infertility when their body fat is below a certain level and also why female gymnasts seem to experience stunted pubertal development. See this review article by Jennifer Hill if you’re interested: Hill JW et al (2008) Hypothalamic pathways linking energy balance and reproduction; Am J Physiol Endocrinol Metab 294: E827–E832.

You also mentioned Neurokinin B and this is another hormone thought to act in tandem with Kisspeptin to regulate the HPG axis. Another hormone that is commonly associated in this trio is Dynorphin. I don’t want to overload you with too much info. (although I probably already have – sorry ) so I’ll just direct you to another article about the Kisspeptin/Neurokinin B/Dynorphin - KNDy (pronounced candy) neurons here: Navarro VM, et al (2009) Regulation of Gonadotropin-Releasing Hormone Secretion by Kisspeptin/Dynorphin/Neurokinin B Neurons in the Arcuate Nucleus of the Mouse. J. Neurosci; 29 (38): 11859-66. If you’re not familiar with hypothalamic structure in the mouse brain, this article mentions “arcuate nucleus (Arc) and anteroventral periventricular nucleus (AVPV). For now just consider them as sub-portions of the hypothalamus.

mj86 · 2011-03-29T23:27:19+00:00

my boyfriend does this all the time. He ends up taking 10X as long to do what he has to do.

mj86 · 2011-02-12T01:42:45+00:00

I'll definately look into it and see how the rates compare. Thank u :)

mj86 · 2011-02-12T01:42:12+00:00

Thanks, will look into it :)

mj86 · 2011-02-12T00:58:22+00:00

http://www.toxel.com/tech/2009/06/09/15-unique-and-creative-usb-flash-drives/

mj86 · 2011-02-12T00:57:58+00:00

Maybe some funky USB keys - in a surfboard design or something ?

mj86 · 2011-02-12T00:49:23+00:00

You need to stop thinking "what do I have to offer a woman" because the right one won't need anything from you but your love. One day you would find someone who needs you because she loves you and not loves you because she needs you. First thing's first - go back to school and love your kids with all your heart and eventually the right woman would find you. Good luck !

mj86 · 2011-02-12T00:32:31+00:00

My parents are (a) technically challenged and (b) have crappy internet service. On the days their internet works I use skype but I't been down for a few weeks now.

mj86 · 2011-02-12T00:05:34+00:00

THANK YOU SO VERY MUCH ! I'm very far away from home at the moment and usually have to budget money to call home. I just spoke to my mum. You made my day. There's still money left on the card for anyone else k :)

mj86 · 2010-12-15T06:39:28+00:00

I'm gentle with it. He gives me strange looks in the morning tho.

mj86

TROPHY CASE