Actually, the last big leptin story was on sexual maturity:
Leptin may be key in turning kids into hormone-filled
teens
Natalie Angier
NEW YORK TIMES NEWS SERVICE
22-Jan-1997 Wednesday
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 pops the hair, the acne, the
secretions, the awkward deposits 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 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, published in the journal Science, lends biochemical
credence to a long-standing 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.
"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.
Dr. Melvin M. Grumbach, a pioneer in puberty research at UC 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."
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 became obese, deprived as they were of
the leptin signal to stop eating. They also turned 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.
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.
'Brain puberty' and fat levels: possible signal of readiness to reproduce
In studies of female mice, injections of the hormone leptin signaled
premature puberty and even reproduction. Here is how such a mechanism might
work in setting off puberty in human females.
Increased body fat signals change
Fat cells proliferate and secrete leptin into blood, from which it reaches
the brain. At a certain concentration, it may theoretically help activate
the pulse generator in the hypothalamous, signaling it to release regular
pulses, about every 90 minutes, of gonadotropin-releasing hormone (GnRH)
Hormones are released
GnRH stimulates the pituitary gland to release luteinizing hormone (LH) and
follicle-stimulating hormone (FSH)
Sexual organs become active
LH and FHS travel through the bloodstream to the ovaries, prompting them to
realease estrogen, the hormone that stimulates breast growth and other
changes of puberty. |
