Here's the NY Times article:
January 7, 1997
Chemical Tied to Fat Control Could Help Trigger Puberty
By NATALIE ANGIER
Into every life a comic disaster must sweep: it's called adolescence. One
minute you are the sovereign of a perfectly respectable, smooth, blade-shaped
body, and the next moment, out pop the hair, the acne, the secretions, the
awkward depositions of fat, the inexplicable taste for tongue studs and
Hermann Hesse.
Like the rest of us, scientists have long wondered why, exactly, children
must become teen-agers. They have sought to identify the chemical signals
that transform body and brain from youthful asexuality to reproductive
maturity. Everybody knows that teen-agers are flooded with hormones like
testosterone and estrogen, but what unleashes those hormonal tides in the
first place?
Now researchers from the University of California at San Francisco propose
that a principal initiator of puberty is leptin, a chemical already famed for
its role in controlling body fat. Leptin was identified several years ago as
a protein secreted by adipose cells that tells the adult body, hey, you are
fat enough, you do not have to keep eating. But its biological role seems to
be weightier still. Dr. Farid F. Chehab and his colleagues found that when
they injected synthesized leptin into normal young female mice, the mice
reached sexual maturity much earlier than rodents injected with inactive
saline solution.
The new research, which appears in the current issue of the journal
Science, lends biochemical credence to a longstanding proposal that puberty
is somehow linked to body fat, particularly in girls. By this notion, called
the "critical fat hypothesis," a girl must reach a certain weight before her
brain feels comfortable that she is capable of sustaining a pregnancy and
thus unleashes the cascade of events culminating in sexual maturity. The
latest results suggest that the brain gauges its nutritional resources and
decides yea or nay on puberty by monitoring blood levels of leptin.
"The neural pathways in the brain need a signal that tells them there are
enough energy stores in the body to turn on reproduction," Chehab said in
telephone interview. "Leptin appears to be the signal that reflects to the
brain the amount of fat the individual has accumulated."
If the rodent results hold up in human studies, they could explain why
chubby girls often go through puberty early and why very thin or athletic
girls are delayed in their onset of menstruation. The researchers also
believe that leptin helps orchestrate puberty in males, though experiments to
demonstrate as much remain to be done.
"Leptin is a gorgeous molecule," said Dr. Rose E. Frisch, a professor
emeritus at the Harvard School of Public Health. "We published a paper back
in 1974 showing that a critical amount of fat was necessary for puberty and
continued ovulation." Since then, she and her colleagues have published more
than 100 papers on the subject, including a study using magnetic resonance
imaging that showed female athletes with low body fat lacked the hormones
necessary for ovulation. It is "very exciting, and very satisfying," Frisch
added, to see in the new leptin findings molecular support for those decades
of research.
Dr. Melvin M. Grumbach of the University of California at San Francisco
said: "This is a really exciting and novel development, opening a wedge in
the study of factors that control the onset of puberty.
But it's important to emphasize these are preliminary mouse studies that
have yet to be shown to have relevance for humans." Grumbach, who did not
work on the current project, is a pioneer in puberty research.
The scientists were inspired to consider leptin as a puberty factor by
previous experiments in which they had worked with genetically altered mice
lacking the leptin gene. Such mice become obese, deprived as they are of the
leptin signal to stop eating; but in addition, they turn out to be sterile.
Chehab and his co-workers reported last spring that they could restore the
rodents' fertility by supplying them with leptin.
In the current experiments, the researchers used normal young mice with the
normal complement of leptin genes. But when the scientists injected the
rodents with extra doses of leptin, two things happened. The mice grew very
lean, as their brains responded to the fake fat signal by prompting them to
eat less. At the same time, they matured early.
Their ovaries and uteri grew larger; their reproductive tracts opened;
their levels of sex hormones soared; and, most persuasively, they began
copulating and bearing young at an earlier age than the saline-treated mice.
"We tricked the brain into believing the body was fatter than it was," Chehab
said.
If leptin proves to be a major puberty signal in humans, it must operate
not by starting something new, but by resuscitating something old. As
Grumbach and others have shown, puberty occurs through a surprising process
of disinhibition. "Puberty in a sense begins in the fetus," he said, with all
the mechanisms necessary for sexual maturity in place in the brain by
mid-gestation. But at 3 years old or so, those neural mechanisms are shut
down, to be revived a decade later at adolescence.
Thus, a baby is in some ways more sexually mature than a child of 6, and in
fact infants do have slightly higher circulating levels of sex steroid
hormones like testosterone and estrogen than do older children.
The neural mechanism that is repressed in childhood is a kind of pulse
generator in the hypothalamus, a structure located at the base of the brain.
The generator operates by secreting batches of a hormone called
gonadotropin-releasing hormone every 90 minutes or so.
That hormonal burst stimulates the nearby pituitary gland, which responds
by secreting hormones of its own, called luteinizing hormone and
follicle-stimulating hormone. These in turn travel through the blood and
reach the gonads, the ovaries in a female, the testes in a male.
At the hormonal tweaking, the gonads give forth the sex hormones, estrogen
or testosterone. And all the secondary sexual characteristics that teen-agers
delight in or despair of -- the swelling of the breasts and hips in girls,
the growth of the penis in boys, the sprouting of pubic hair and acne in both
-- result from the might of sex hormones.
The revival of the hormonal pulse generator of the hypothalamus is
essential to the onset of puberty, and in fact to the reproductive system of
the adult. Presumably, leptin fits into this act of disinhibition, but where
and how the protein works its black magic have yet to be determined. As with
adolescence, the difficult part is just beginning.
Henry |
