Hello!

There has been many talks about the fact that prepubertal castration
(or inherited hypogonadism), both in humans and other animals, are
often associated with prolonged physical growth wich often lead to
gigantism later in life. This is because epiphyses in the longbones
fail to close due to abscense of sex hormones during puberty. The
famous Italian castrati singers of the past (17th - 19th century) were
often reported to reach unusual heights and especially striking
proportions were the longbones in the arms and legs were
unproportionally long. However, what is the exact mechanisms behind
all this? Does prepubertal hypogonadism really lead to uncontrolled
and continuing growth? What are the factors worth considering here?
Did castrati really continued to grow all their lifes?? An
invistigation done by German medics in 1910 on the Rumanian skopzy
sect showed that one individual castrated at 8 years of age, even at
35 had open epiphysis and thereby continued to grow! This was
collaborated by other studies (Male soprano Javier Medina from Mexico,
hypogonadal since childhood, finally managed to stop his growth at 33
only after taking hormones). However, many castrati singers still were
of average or even lesser height even in old age. How is this
possible? What can studies on animals tell us about this? If these
individuals really ever ceased to grow, then at what age and what
point in life? Why did they (if they ever did) cease to grow if there
is no hormones to close the epiphysis? Other factors apart from
male/female hormones that can end the growth of the skeleton? Anything
else worth mentioning?

Fabulous question, Musico. The castrati are a fascinating part of
social, medical and music history. I heard a recording of Alessandro
Moreschi, the "Last Castrato" when I was studying music in university,
and I have been fascinated with the phenomenon ever since.

Your grasp of physiology is pretty good, but you are missing a very
straightforward explanation for both the fact that some castrati did
not grow excessively, and for the individual variation in heights
amongst them.

You are probably correct that epiphyseal closure is mediated by the
sex hormones, but that is a drastic oversimplification of the process.

First off, the castrati were not without sex hormones! That may come
as a surprise to you, but it is true. Many other parts of the body are
capable of producing and releasing sex hormones into the body, for
example the adrenal gland and even fat cells. After the surgical
removal of the testicles, the amount of sex hormone production
increases.

If the testicles are removed before puberty, as was the case for most
castrati, there is little change in the hormonal miliieu, at least as
regards things that affect epiphyseal closure. Once puberty is
reached, however, the production from the hypothalamus Gonadotropin
Releasing Hormone (GnRH) is not necessarily impaired. Neither is the
response of the pituitary gland to this substance, resulting in the
production from the pituitary of the sex-hormone-releasing-hormones,
called follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
which act on the tissues of the body to produce the sex hormones. This
is the mechanism of puberty.

Now, while the adrenal gland and other tissues tend to be relatively
resistant to stimulation by FSH and LH, at least as compared to the
testicles, there is some evidence that these tissues increase their
production of sex hormones in the absence of the gonads. Part of that
may be related to increased sensitivity to LH and RH.

Even more importantly, the castrati did not depend solely upon the
adrogens (for example: testosterone) produced in their (now missing)
testicles for closure of their epiphyses. Oh no! If that were the
case, then women, with relatively lower concentrations of androgens
compared to men could be expected to tower over men by age twenty or
so. Obviously, that doesn't happen. Estrogens are not only capable of
mediating epiphyseal closure, but they are produced (in the form of 17
beta estradiol) FROM the androgens. Additionally, the same tissues
that produce androgens in the castrated male also produce estrogens.
It is a little known fact (outside of the medical profession) that men
and women both have circulating estrogens and androgens. So the
castrati might have has lower levels of circulating sex hormones, but
they were far from having none at all.

There would certainly be expected to be individual variation in the
levels of sex hormones among castrati, and that alone could account
for the fact that some of them grew to apparently normal heights, and
some were taller than expected. but there is another reason they
didn't keep growing: growth hormone!

While the presence of sex hormones may force epiphyseal plates to
close, leaving them open, by itself, does not ensure continued growth.
For growth to occur, growth hormone must be present. Luckily for most
castrati, levels of growth hormone decrease throughout life. Otherwise
more of them would probably have suffered from gigantism.

Growth Hormone (GH) is produced by the pituitary in response to a
substance released from the hypothalamus called Growth Hormone
Releasing Hormone (GHRH). It is GHRH that decreases after puberty,
resulting in a decrease in GH production, rather than some innate
tendency of the pituitary. Not only that, but the hypothalamus puts
out another substance, called Somatostatin, that is a potent inhibitor
of pituitary GH production, and its concentration INCREASES after
puberty. This is a mechanism that really puts the brakes on growth
after puberty. It has probably evolved because the consequences of
unrestricted growth are so severe. People who suffer from gigantism
(excessive GH with unclosed epiphyses) have a lot of health problems.

Autopsies on people who were castrated before puberty might very well
show open epiphyses in some cases, up to almost any age at death. Just
because the epiphyses were open, however, doesn't mean these people
were still growing; only that they had the POTENTIAL to grow.

Thanks for the interesting question!

Alan Kali

Google answers doesn't have a "Preview" button (hint, hint Google) so
I cannot look over the finished product. I always find errors when I
read a long post after I hit the button. Here they are.

Errata:

Paragraph 3 should clarify that sex hormone production OVERALL does
not increase after castration, but sex hormone production from
non-gonadal tissues increases, sometimes quite drastically.

Paragraph 5 omitted to mention that the hormonal antecedents of
puberty, including production of GnRH, FSH and LH occur during the
time of puberty whether or not the gonads are present to respond to
them. While the outward sings of puberty may be absent, the internal
mechanism continues. In fact, antecedant hormone levels may be
drastically INCREASED since the normal feedback inhibition by the sex
hormones does not occur. Like revving an engine in neutral.

Paragraph 6 should end. "... to LH and FSH". LH is a commonly used
medical abbreviation for "left hand" in addition to standing for
Luteinizing Hormone. I guess I got carried away and wrote RH (the
medical abbreviation for "right hand") out of sheer force of habit.

That's all.

Alan Kali

Thank you, Alan, for this wonderful and thoughtful explanation; I
believe you indeed managed to take up almost everything our medical
science knows about this topic up to date. Of course, there is still
some things we might be unaware of, as no particular growth-study has
been made on these individuals.

Anyway, we can still try to experiment with what we know, and use our
own immagination in order to shade some light on the matter.
Basically, if I remember correct, the shortest castrati were often
plumpy and feminine, whilst those higher were often more "masculine"
in appearance. This was the case with Moreschi (short; plumpy) and
many others.

What it could then tell us, as you also point out, is that those
castrati who were overweight, and whoes fatcells produced a lot of
estrogen (wich often lead to development of the breast tissue), led to
that the estrogen might either supress HG or end the growth of the
bones on a permanent level. However, I feel that your statement that
the HG falls during puberty in all sexes doesn`t take into
consideration the feedback mechanism that exists between
estrogen>testosteron>HG.

Also, what about the "prepubertal-dip" phenomena? Excessive growth
during puberty is triggered by the rise in sex hormones, wich also put
an end to the growth and what I believe, suppress the HG production.

Well, anyway, many thanks for your very useful explanation! I now
believe I have a better insight into the subject; I am also pleased to
have some of the statements I previously learned of a "heresay"
confirmed by you.

Sincerely,

Muscio-ga.

Musico,

Growth is really complicated, and I have certainly oversimplified. I
didn't approach the "growth spurt" in castrati because I have no idea
if it occurred. We're getting into an area where knowledge is scanty.
You can't really do an experiment to see what happens when children
reach puberty without sex hormones; it would be unethical in the
extreme. We have to extrapolate from the history of the castrati and
current information about people with hormonal disorders.

One thing I am fairly sure of is that you don't require sex hormones
to shut down growth hormone production after puberty. If you did, then
all people with a lack of sex hormones would develop gigantism (if
their epiphyses stayed open) or acromegaly (if their epiphyses
closed). This is certainly not the case.

The somatic-hypothalamic-pituitary feedback mechanisms are terribly
complex in normal indivduals. Introducing an abnormality further
complicates matters. Until musical tastes (and certain legal, ethical
and social principles) change drastically, we are left without a
population to study. Until then, there is necessarily an element of
speculation in this area.

Alan Kali