The Triggers That Start Puberty.
Introduction
Derived from the Latin word Pubertas which means "age of maturity, manhood and associated with the word Pubes meaning full-grown and manly", puberty is not a single time event and takes a long time throughout an individual's life [1]. Puberty can also be defined as the ability to successfully reproduce and pass down the genetic codes to an offspring. Factors that influence the timing to puberty are: hormonal, genetics, nutritional and environmental [1,2]. Puberty is thus extremely important for humans to carry on our legacy and humanity's survival, so the important questions are when, why and how does puberty start?
From left to right: Adrian, myself, Manon, Hugo, Margot and Marc-antoine. All of us, at their own time and due age, will start puberty.
In a female, to be able to demonstrate fertility can be a bit blurry. For example, the age of menarche (when a woman has her first menses) does not mean ovulation has occurred [1]. It is sufficient for the endometrium layer to be able to accept the blastocyst and have a successful implantation as it would make sense for the endometrium to be developed first before the body starts to ovulate. This can take up from months to years to be able to ovulate and have a successful fertilization with the spermatozoa. However, menarche is definitely a sign of the onset of puberty [1]. The age of the first ovulation is difficult to observe but is found to be in relation when the body can carry out pregnancy without dangerous side effects [1,2]. Meaning that the body knows somehow that it can perform the heavy metabolic cost of pregnancy and lactation which are high in terms of energy [1]. Ovulation is also in conjunction with body size and weight as more will be explained later.
In a male, the start of puberty is to be able to demonstrate an individual's first ejaculation [1,2]. However, it does not mean fertility as during the first ejaculation it is generally azoospermic. After some time, there will be sperm present but again it does not demonstrate fertility as you need at least 15 million sperm per millilitre and at least 2 millilitres to be able to fertilize an egg successfully. Having less than normal sperm count is considered to be oligozoospermic and hence the individual is not fully fertile. When the age of having the minimum threshold of sperm count has been reached, the individual has thus achieved fertility [1,2].
Azoospermic: a condition when there is no sperm in the semen [1].
Blastocyst: is the outcome of an oocyte (egg) and a spermatozoa successful fertilization. A ball of cells of about 64 cells and that is 5-7 days old, the first differentiation has occurred. The inner cell mass is now pluripotent and trophoblast cells are surrounding the cell mass [1].
Endometrium: the tissue that lines the uterus, it is responsible for the site of implantation of the blastocyst and if fertilization did not occur it is the layer of tissue that gets shed away [1].
Menses: discharge from the uterus along with blood. A sign of puberty in a young woman [1].
Oligozoospermic: low sperm count with a low concentration [1].
The Hypothalamus and Puberty
Before I go on, there is a need to briefly talk about the hypothalamus and the development of the surge centre. The hypothalamus regulates the onset of puberty and many questions arise from it [1-3]. How does the hypothalamus know when to start puberty, what triggers it and how? It all depends on the hypothalamic neurons to produce sufficient quantities of the Gonadotropin-Releasing Hormone (GnRH) which will promote and support gametogenesis [1-3]. The important bit is that the hypothalamus functions differently between males and females whereas in males there is an absence of positive feedback of Oestrogen to act on the surge centre [1]. So, if the release of GnRH promotes and support puberty, what causes the hypothalamus to start releasing GnRH in the first place and most importantly why now and why not later during the years? Why is there a difference between each individual?
The surge centre development is different between males and females. In males, the Testosterone from the foetal testis "de-feminizes" the brain through inhibiting the surge centre [1,3]. Testosterone goes through the blood-brain barrier and is converted into Oestradiol (an Estrogen steroid hormone) by the aromatase enzymes, hence the surge centre does not develop [1,3]. In a funny set of outcome, Oestradiol is responsible for this process!
Credit: Senger 2005.
In females, the Oestradiol released from the foetal ovaries is bound to α-fetoprotein which prevent Oestradiol to cross the blood-brain barrier [1,3]. Hence the lack of Oestradiol in the brain will not create de-feminization of the brain and the development of the surge centre will occur.
Credit: Senger 2005.
Okay so females have a Surge Centre and males do not, so what?
Males and females will display similar tonic basal concentration of a constant GnRH concentration that is controlled through negative feedback. However, for females, there will be a pre-ovulatory burst which is from the surge centre. During puberty, the surge centre in a woman will play a major role and is important for ovulation.
The surge centre is sensitive to positive feedback and will then release high amplitude, a high-frequency pulse of GnRH for a short period of time when Oestrogen has reached a certain level [3]. The reason of Oestrogen reaching a level is from the granulosa cells converting androgens to Oestrogens after the dominant mature follicle (at its tertiary antral stage) there is huge positive feedback exerted by a large increase in Oestrogen output [1]. When there is a surge burst consider the tap to be fully flowing for a short period of time instead of the constant and few drops which represents the tonic basal layer [1,3]. What is interesting is that Oestrogen act in the negative feedback meaning that more Oestrogen, less Follicular Stimulating Hormone (FSH) and Luteinizing Hormone (LH) and hence less Oestrogen [1]. But that is not the case. Yes, there is a negative feedback, however, the more the single dominant follicle grows and matures the more Oestrogen it is releasing as more androgens are released from the thecal cells and the more there is an androgen conversion to Oestrogen. This will go on until there is a reached Oestrogen threshold and a sudden positive feedback is initiated releasing an LH surge and soon ovulation will occur. The surge centre is thus extremely important in a woman going through puberty and for the rest of her life until she will be menopausal [4].
Credit: Husvéth F, Egyetem D, Egyetem N, Egyetem P.
Large amount of oestrogen and androgens (from the thecal cells - to be converted) delivered from the granulosa cells from the mature tertiary follicle to create a positive feedback on the surge centre.
Credit: Husvéth F, Egyetem D, Egyetem N, Egyetem P.
Gametogenesis: The process in which cells undergo meiosis to form gametes [1].
GnRH: gonadotropin-releasing hormone moves through the short bloodstream pathway (hypophyseal portal system) to the anterior pituitary gland. There, it binds to the gonadotropic cells. These will produce gonadotropins hormones, such as the follicle-stimulating hormone (FSH) and luteinizing hormone (LH) [1].
Hypothalamus: located at the base of the brain plays a crucial role in releasing hormones that will act on the anterior and posterior pituitary gland. Helps in regulating body temperature [1].
Positive feedback: The enhancing or amplification of an effect by its own influence, such as a baby suckling on its mother will cause the mother to release more milk [6].
Negative feedback: The diminution of an effect by its own influence, such as a high level a hormone A will cause a loop that will prevent further secretion of hormone A [6].
What starts the onset of puberty?
So far we talked about how the male's hypothalamus is de-feminized and that the woman's hypothalamus is feminized and contains a surge centre. We still have important questions to answer, if the hypothalamus is responsible for the onset of puberty such as the process of releasing GnRH (as it promotes and supports puberty), what causes the hypothalamus to start releasing GnRH in the first place? Why now and why not later during the years? Why is there a difference between each individual?
The onset of puberty is not only limited to the gonads or anterior pituitary glands as puberty depends on the release of gradual GnRH in sufficient quantities. In other words, it comes down to the maturation of the hypothalamus [1,4-6]. Before puberty, the GnRH neurons in the hypothalamus and the tonic centre are highly sensitive to negative feedback by the levels of Testosterone and Oestrogens. Meaning a slight rise in the concentration of these hormones will result in an immediate negative feedback which will bring down those levels. Those hormones being suppressed all the time do not affect secondary sexual characteristics. The surge centre is also not yet responsive to Oestrogen [1].
Now things are getting interesting. During the pubertal transition, the sensitivity of the GnRH neurons for the negative feedback starts to drop and slowly decline [6]. A declined sensitive negative feedback thus results in an increase of GnRH concentration, from the tonic centre, in the bloodstream (meaning as time goes you need more GnRH to initiates the negative feedback).
The next question is; what causes the tonic centre to lose its sensitivity to negative feedback? To answer this question it is best understood in females rather than males. There is a clue with the amount of energy available that a person contains, such as the amount of fat a person has. As we talked earlier, pregnancy and lactation require a huge metabolic cost [1]. At the end of the day another human being is being made from the mother's metabolic cost and there is a need afterwards to create food for that baby that will guarantee its success in its development. Hence, a certain amount of fat reserves are needed before the brain decides it is time to initiate puberty and develop its reproductive organs. How disastrous would it be if a woman's body got pregnant but the body itself cannot guarantee a fair chance of development which could endanger the mother's life in the process? It is not to say that fatness alone is responsible for promoting puberty as young obese girls are not into any pre-pubertal stages. Reaching a threshold of body size and condition such as a body mass index can also be a factor. The fatness and other metabolic signals may be the reason why there is a loss in sensitivity and initiation of GnRH pulse and that may be affected by the concentration of glucose, leptin or fatty acids in the blood [1]. A lot of uncertainty but it does make sense.
Different metabolic signals may act differently on the GnRH neurons to release GnRH, these could be a reason when they are abundant.
A very interesting graph of the mean age of young woman having their first menarche during the past 180 years. Notice how it decreases in age over time as more countries improved on their quality and quantity of food. Hence, young woman were more healthy and had sufficient energy and fat stores to start puberty at a younger age. It is important to note that a critical weight of 47 kg must be obtained to start puberty, however that is not always the case.
Take home message
Puberty is a gradual process that starts at different ages for different individuals. The Gonadotropin-Releasing Hormone (GnRH) must somehow lose its sensitivity to negative feedback at the tonic centre to Oestrogen for females and Testosterone for males. The surge centre is developed in females as the male hypothalamus has been de-feminized and the surge centre must have a positive feedback response to oestrogen. Nutrition and body mass index play a key role in the onset of puberty. Pinpointing key factors is difficult as there are many scientific papers out there that talks about certain foods are responsible for the earlier onset of puberty. Genetics and different ethnicity could also be a factor and why some individuals start earlier or later. The environment an individual has been exposed to its whole life or the environment surrounding the mother during pregnancy and the child's growth could also be a factor. So how much of these factors play a role is also unknown, still, the onset of puberty is an unknown and interesting topic.
Published 30th January 2019. Last reviewed 30th December 2021.
Reference
1. Drake RL, Vogl AW, Mitchell AWM. Gray’s Anatomy for Student. 3rd ed. Philadelphia: Churchill Livingston Elsevier; 2015. ISBN: 978-0-7020-5131-9.
2. University Lecturer. Lecture 8: Puberty. Department of Animal Sciences University of Wisconsin-Madison. http://www.ansci.wisc.edu/jjp1/ansci_repro/lec/lec8/lec8out.html. Updated February, 1998. Accessed December 3, 2018.
3. Husvéth F, Egyetem D, Egyetem N, Egyetem P. Physiological and reproductional aspects of animal production. Digitalis Textbook Library. https://www.tankonyvtar.hu/en/tartalom/tamop425/0010_1A_Book_angol_05_termeleselettan/ch12s03.html. Updated 2011. Accessed December 3, 2018.
4. Dr. Damien Paris, 2018. Menopause & Hormone Therapy Replacement. Lecture given at James Cook University. Tuesday, 9 October 2018.
5. Johnson MH. Puberty and the Maturation of the Hypothalamic-Pituitary-Gonadal Axis. Essential Reproduction. 6th ed. Malden, Massachusetts. Blackwell Publishing, Inc; 2007;133-145.
6. Deneris A, Huether SE. Structure and Function of the Reproductive System. In: Dennison B, ed. Pathophysiology: The Biologic Basis for Disease in Adults and Children. 5th ed. St Louis, Missouri. Elsevier Mosby; 2006;735-770.
Additional source of information:
Jones RE, Lopez KH. Human Reproductive Biology. 4th ed. Academic Press, 2013. eBook ISBN: 9780123821850.
Kerr J. Functional Histology. 2nd ed. Melbourne, Australia. Elsevier Mosby, 2010. ISBN 9780729538374.
Marieb EN, Hoehn K. The Reproductive System. In: Beauparlant S, ed. Human Anatomy & Physiology. 9th ed. Boston, USA. Pearson Education, Inc; 2013;1018-1094.
