SYR: How sheep can help us understand why girls are reaching puberty at younger ages

michelle-bedenbaughThis guest post is the second written ~ dint of. Michelle Bedenbaugh, a Ph.D. observer in the Physiology and Pharmacology Department at West Virginia University. Check off her first post on the benefits of using comprehensive animal models to study reproduction. It is in addition part of our Speaking of Your Research concatenation of posts where scientists discuss their avow research. In this post, Michelle discusses more of the cells and signaling pathways that are momentous for controlling the timing of puberty and for what reason the use of sheep as a fashion is beneficial for this type of examination. If you would be willing to scribble a guest article for Speaking of Research, please juxtaposition us here.

For those of you who require been watching the news in the United States across the past 5-10 years, you be the subject of probably heard a few discussions not far from the fact that girls are reaching puberty at younger ages.  In the 1980s, girls normally reached puberty right and left the age of 13.  In 2010, the medium age of girls reaching puberty had dropped to 11 and has as continued to decline.  Reaching puberty at earlier ages is associated with several adverse health outcomes, including polycystic ovary syndrome (PCOS), metabolic syndrome, corpulency, osteoporosis, several reproductive cancers and psychosocial straits.  The public and researchers be favored with pointed fingers at several potential culprits, including ~y unhealthy diet, chemicals that disrupt the body’s natural hormonal environment, and an individual’s genetic leaning to disease.  In reality, a union of factors have probably led to the grow less in the age at which girls hold forth puberty, but I don’t inadequacy get into a discussion about these factors today.  Instead, I lack to talk about some of the signaling molecules in the corpse that these factors may be influencing to like the initiation of puberty.

As through many processes in the human dead ~, the brain plays a critical role in the mastery of reproduction and the timing of puberty.  Within a particular area of the brain called the hypothalamus, distinct populations of neurons (specialized cells in the brain) breathe that control reproduction.  The mode of exercise of these neurons is influenced ~ dint of. various factors that are communicated from other genius of the body and outside environment to the brain, including nutritional status, concentrations of sex steroids (like estrogen and testosterone), genetics, and various other external factors.  All of these factors reveal the brain when an individual has obtained the qualities requisite to successfully reproduce and therefore suffer pubertal maturation.  Gonadotropin-releasing hormone (GnRH) neurons fix in the hypothalamus are the ultimate step in this chain of intercourse and are essential for the admission of puberty.

A GnRH neuron present in the hypothalamus.

A GnRH neuron gratuity in the hypothalamus.

Most of these nutritional, hormonal, genetic and environmental signals are not directly communicated to GnRH neurons.  Instead, they are conveyed end other types of neurons that therefore relay this information to GnRH neurons that either stimulates or inhibits the set at liberty of GnRH.  Because GnRH is a signaling ultimate particle that ultimately stimulates the maturation of staminate (sperm) and female (egg) gametes, stimulating GnRH in transfer stimulates reproductive processes while inhibiting GnRH inhibits reproductive processes.  The pure balance of stimulatory and inhibitory inputs is needed in opposition to GnRH to be released and during the term of puberty to be initiated.  Consequently, whether or not stimulatory inputs signal to increase GnRH too early, puberty will occur earlier, which may decision in several of the health concerns that were mentioned over later in life, including reproductive cancers and psychosocial poverty.  In contrast, if inhibitory inputs fill up the release of GnRH, puberty will never occur and result in infecundity.

My research looks at some of these stimulatory and prohibitory inputs and how they communicate by each other, as well as by GnRH neurons.  Two of the stimulatory signaling molecules that we research are kisspeptin and neurokinin B (ludicrous names, I know).  We too study dynorphin (another funny name), a molecule that inhibits GnRH release.  These three molecules be possible to all individually affect GnRH release and by consequence reproduction.  However, the really chilling thing about these three molecules are that they are positively present together in a special exemplar of neuron that is only set in one small and highly particular area of the hypothalamus.  Because these neurons hold kisspeptin, neurokinin B, and dynorphin, they are repeatedly called KNDy (pronounced “candy”) neurons.  The truth that kisspeptin, neurokinin B, and dynorphin are totality present in these KNDy neurons contemporaneously allows for them to communicate presently and affect each other’s dispensation.  This communication then ultimately affects the discharge of GnRH.  Before puberty, inhibitory inputs, like dynorphin, dominate and don’t abate for adequate amounts of GnRH to have ~ing released to stimulate reproduction.  As each individual matures, stimulatory inputs, like kisspeptin and neurokinin B, institute to outweigh inhibitory inputs, and GnRH be able to be released in adequate amounts to encouragement reproductive processes.  Below is a figure that summarizes how we think all of this works within the body.  However, there is still a piece of land that we don’t know relative to how kisspeptin, neurokinin B and dynorphin interact through each other that is waiting to have ~ing discovered!

Hypothesized model for the initiation of puberty. (1) Internal and external factors are communicated to the body. (2) Next, these factors are relayed through various signaling pathways to stimulatory and inhibitory molecules present in neurons located in the hypothalamus. (3) Stimulatory and inhibitory molecules travel to GnRH neurons and affect the release of GnRH. (4) GnRH stimulates reproductive processes that are critical for the initiation of puberty. (5) Once all of the proper conditions are met, reproductive maturity is attained.

Hypothesized model for the opening of puberty. (1) Internal and apparent factors are communicated to the carcass. (2) Next, these factors are relayed from one side various signaling pathways to stimulatory and prohibitory molecules present in neurons located in the hypothalamus. (3) Stimulatory and prohibitory molecules travel to GnRH neurons and impress the release of GnRH. (4) GnRH stimulates reproductive processes that are dubious for the initiation of puberty. (5) Once altogether of the proper conditions are met, reproductive completion is attained.

To complete all of these studies, we conversion to an act sheep as our model.  I understand what some of you are judgment.  “How in the globe would sheep serve as a untarnished model for how puberty is initiated in humans?  I don’t have an opinion I am similar to a sheep at everything!”  In fact, sheep are actually an excellent model in which to fare this research.  The signaling pathways that affect the release of GnRH in sheep are actual similar to the signaling pathways in humans, and in some cases, are even more similar to the human pathways than the pathways not heedless in mice or rats.  In humans and sheep, neurokinin B has solely been found to stimulate GnRH discharge.  However, in rodents, there desire been reports of neurokinin B both stimulating and inhibiting GnRH release.  Since neurokinin B is human being of the main signaling molecules that we study, using sheep in the room of mice or rats is in addition beneficial for modeling what is occurring in humans.


Because we be the subject of to collect several blood samples from the sheep in precept to measure hormone concentrations, having some animal with a larger blood whirl is also advantageous.  Several hormones in the dead ~ (including GnRH) are released in a pulsatile air, meaning one minute GnRH concentrations are lofty and a few minutes later they are humble.  Therefore, in order to appropriately rule GnRH, blood samples need to have ~ing taken every 10-12 minutes on this account that several hours.  This is not feasible in rodents.  If you took disposition samples as frequently in rodents being of the cl~s who is possible in sheep, you would danger killing the animal.  Some scientists who application rodents as their research model essay to get around this issue through taking blood samples less frequently.  However, this shift their hormone measurements are less faithful.

These are just a few of the numerous reasons why we conduct our exploration in sheep (to learn more from one place to another the advantages of using sheep and other comprehensive animal models to conduct research involving copy, see my previous post).

While principally people (including myself) do not take notice back fondly on our awkward pubertal years, I actually love studying the signaling pathways the body uses to determine when it is handy to successfully reproduce.  We get discovered quite a bit over the after few decades concerning how different inward and external factors affect pubertal maturing, but there are still so ~ people unknowns left to be determined.  I be turned forward to hopefully discovering some of these unknowns and improving our mind of how puberty is initiated in the pair humans and livestock species.

Michelle Bedenbaugh

Accutane is at the fetus – subject to no circumstances should a woman prevail upon pregnant while taking this treatment.

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