Some Details on the Function of the Hypothalamus-Pituitary-Ovaries
Axis
Dr. Nelson Soucasaux, Brazilian gynecologist
The amazing cyclical feature that characterizes the ovarian function
and, therefore, the female endocrine physiology and the menstrual cycle,
is due to an extremely intricate functional interaction between the ovaries
and the hypothalamus-pituitary system, by means of feedback mechanisms.
(The hypothalamus is the part of the brain that the pituitary is attached
to. The pituitary or hypophysis is the gland that commands most of the other
endocrine glands in the body. The pituitary function depends almost entirely
on the hypothalamic control. The hypothalamus, in turn, is constantly receiving
influences from other parts of the brain. It is just for that reason that
we speak on the hypothalamus-pituitary system.)
Not only the hypothalamus-pituitary system controls the ovarian function,
but the ovarian function also controls the hypothalamus-pituitary system.
There is a continuous mutual interaction between both and it is just by
means of this highly intricate interaction that the existence of the ovarian
cycle is made possible. The main factors responsible for the function of
the so-called hypothalamus-pituitary-ovaries axis are the hypothalamic neuro-hormones
and the pituitary and ovarian hormones.
The follicle stimulating hormone (FSH) and the luteinizing hormone (LH)
are the pituitary gonadotropins that control most of the ovarian function.
The release of these gonadotropins by the pituitary is controlled by the
hypothalamus by means of a neuro-hormone known as Gn-RH (gonadotropin releasing
hormone, which is the same for the FSH and the LH). The estrogens produced
by the ovaries under the FSH and LH command exert, in turn, negative and
positive feedback actions upon the hypothalamic neural centres responsible
for the Gn-RH production. A negative feedback action is characterized by
an inhibiting effect upon some of these centres, while a positive feedback
action produces a stimulation of other hypothalamic centres. In this way,
the levels of estrogenic production throughout the ovarian cycle indirectly
control the pituitary release of FSH and LH. On the other hand, the ovarian
estrogenic production depends on the FSH and LH stimulation.
The hypothalamus-pituitary system's reaction to the feedback exerted
by the estrogen levels along the menstrual cycle exhibits an ambivalent
pattern which is typically female. A regimen of negative feedback predominates
along almost all of the cycle; in this way, as the estrogen levels increase,
the gonadotropic secretion is reduced. However, when a growing ovarian follicle
reaches its mature stage, and begins the production of heightened estrogen
levels within a specific "critical" threshold and duration, the
opposite effect takes place and, by means of a positive feedback, the pituitary
ovulatory peak of LH is released.
This is due to the action of different hypothalamic neural centres involved
in this highly intricate and precise mechanism. They are: 1) a tonic center
that controls the basal secretion of FSH and LH by the pituitary throughout
almost all of the cycle; this centre is sensitive to the negative feedback
action of the circulating estrogens; 2) a cyclical center, the one that
triggers the pituitary release of the LH ovulatory peak; it is just upon
it that the high estrogen levels produced by the mature ovarian follicle
exerts a positive feedback action.
Now, let us say some words about the basic patterns of the FSH and LH
pituitary secretion along a typical ovulatory cycle. During most
of the cycle, the FSH exhibits a basically steady pattern of secretion with
two slight elevations. The first elevation arises on the last days of the
cycle that terminates and lasts up to the first days of the new cycle that
begins; the second one is transitory and coincides with the LH ovulatory
peak. These two cyclical elevations of the FSH are supposed to stimulate
more effectively the growth of follicles that are in their earlier stages
of development. The LH exhibits a tonical steady pattern of secretion along
most of the cycle except at the pre-ovulatory period, when a great amount
of this gonadotropin is suddenly released in a very short period of time
constituting the LH ovulatory peak. Its purpose is just triggering ovulation
and stimulating the beginning of the corpus luteum formation. This peak
of LH does not occur in the anovulatory cycles.
The ovarian processes of follicular maturation, ovulation, formation
of the corpus luteum and synthesis of the sexual hormones are under the
control of the pituitary gonadotropins. Only the beginning of the first
stage of follicular growth does not depend on the gonadotropic stimulation,
being a process which the ovary, all by itself, sets in motion. From this
stage on, in order to proceed their development up to the stage of mature
follicle and produce good estrogen levels, the ovarian follicles depend
on the FSH and LH stimulation. On the other hand, ovulation and formation
of the corpus luteum depend on the LH ovulatory peak.
In the process of follicular growth and estrogen synthesis the LH stimulates
mostly the theca cells, while the FSH stimulates mostly those of the
granulosa. (Each growing ovarian follicle is formed by an oocyte surrounded
by several layers of granulosa and theca cells. The theca cells, under the
LH stimulation, produce mostly androgens, while the granulosa cells, under
the FSH stimulation, turn these androgens into estrogens.) There are reports
that the estrogens produced by the follicles may provide some help in these
processes, since they seem to stimulate the multiplication of the granulosa
cells and increase their responsivity to the FSH.
Even so, in spite of that small collaboration of the estrogens in the
process of follicular growth, the FSH and the LH are, undoubtedly, the most
important hormonal factors responsible for the follicular maturation and
the ovarian estrogen synthesis. As an ovarian follicle proceeds its development,
the quantity of FSH-receptors contained in its granulosa cells also increases
and, for that reason, the follicle becomes more and more sensitive to the
FSH stimulation. In this way, the follicular maturation accelerates and
its estrogen production becomes higher, since it is under the action of
the FSH that the granulosa cells turn the androgens produced by the theca
cells into estrogens.
In the mature, pre-ovulatory follicle, the granulosa cells also become
receptive to the LH. This happens because the action of the estradiol and
the FSH produces a great increase of LH-receptors in these cells. In this
way, immediately after ovulation which is triggered by the pituitary
peak of LH the luteinization of the ruptured follicle takes place,
giving rise to the corpus luteum. The corpus luteum produces progesterone
and also estrogens, and is formed by the granulosa-lutein cells and the
theca-lutein ones. Though possessing a considerable intrinsic capacity of
self-regulation, the corpus luteum also depends on normal LH levels for
its maintenance along its 12 to 14 days of duration throughout the second
phase of the menstrual cycle.
The blockage of most of the ovarian function and the resulting
suppression of ovulation induced by the use of the hormonal contraceptives
is just based on the medicinal creation of a negative feedback upon the
hypothalamus-pituitary system. The estrogens and progestins (synthetic progesterones)
contained in the "Pill" produce an inhibition of this system,
resulting on several alterations of the normal patterns of FSH and LH secretion
by the pituitary. During the use of the hormonal contraceptives the basal levels
of FSH and LH are slightly reduced and the ovulatory peak of LH is abolished.
As a consequence, the growth of the ovarian follicles is interrupted in
their earlier stages of development, no one of them reaching the stage
of mature follicle and ovulation is suppressed.
The article above is an adapted excerpt from my book "Os Órgãos
Sexuais Femininos: Forma, Função, Símbolo e Arquétipo"
("The Female Sexual Organs: Shape, Function, Symbol and Archetype"),
published by Imago Editora, Rio de Janeiro, 1993. For more information on
the book, see page http://www.nelsonginecologia.med.br/orgaos.htm
at my website www.nelsonginecologia.med.br
.
Copyright Nelson Soucasaux 1993, 2005
_______________________________________
Nelson Soucasaux is a gynecologist dedicated to clinical, preventive
and psychosomatic gynecology. Graduated in 1974 by Faculdade de Medicina
da Universidade Federal do Rio de Janeiro, Brazil, he is the author of several
articles published in medical journals and of the books "Novas Perspectivas
em Ginecologia" ("New Perspectives in Gynecology")
and "Os Órgãos Sexuais Femininos: Forma, Função,
Símbolo e Arquétipo" ("The Female Sexual Organs:
Shape, Function, Symbol and Archetype"), published by Imago Editora,
Rio de Janeiro, 1990, 1993. He has been working in his private clinic since
1975.
Web site (Portuguese-English): www.nelsonginecologia.med.br
Email: nelsons@nelsonginecologia.med.br