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SECTION IV
Endocrine & Reproductive Physiology
slowly declines with advancing age, but the ability to produce
viable gametes persists.
In both sexes, the gonads have a dual function: the produc-tion of germ cells
(gametogenesis)
and the secretion of
sex hor-
mones.
The
androgens
are the steroid sex hormones that are
masculinizing in their action; the
estrogens
are those that are
feminizing. Both types of hormones are normally secreted in
both sexes. The testes secrete large amounts of androgens, prin-
cipally
testosterone,
but they also secrete small amounts of
estrogens. The ovaries secrete large amounts of estrogens and
small amounts of androgens. Androgens are secreted from the
adrenal cortex in both sexes, and some of the androgens are
converted to estrogens in fat and other extragonadal and extra-
adrenal tissues. The ovaries also secrete
progesterone,
a steroid
that has special functions in preparing the uterus for pregnancy.
Particularly during pregnancy, the ovaries secrete the polypep-
tide hormone
relaxin,
which loosens the ligaments of the pubic
symphysis and softens the cervix, facilitating delivery of the
fetus. In both sexes, the gonads secrete other polypeptides,
including
inhibin B,
a polypeptide that inhibits follicle-
stimulating hormone (FSH) secretion.
The secretory and gametogenic functions of the gonads are
both dependent on the secretion of the anterior pituitary
gonadotropins, FSH, and luteinizing hormone (LH). The sex
hormones and inhibin B feed back to inhibit gonadotropin
secretion. In males, gonadotropin secretion is noncyclic; but
in postpubertal females an orderly, sequential secretion of
gonadotropins is necessary for the occurrence of menstrua-
tion, pregnancy, and lactation.SEX DIFFERENTIATION
& DEVELOPMENT
CHROMOSOMAL SEX
The Sex Chromosomes
Sex is determined genetically by two chromosomes, called the
sex
chromosomes,
to distinguish them from the
somatic chromo-
somes (autosomes).
In humans and many other mammals, the
sex chromosomes are called X and Y chromosomes. The Y chro-
mosome is necessary and sufficient for the production of testes,
and the testis-determining gene product is called SRY (for sex-
determining region of the Y chromosome). SRY is a DNA-
binding regulatory protein. It bends the DNA and acts as a trans-
cription factor that initiates transcription of a cascade of genes
necessary for testicular differentiation, including the gene for
müllerian inhibiting substance
(
MIS;
see below). The gene for
SRY is located near the tip of the short arm of the human Y chro-
mosome. Male cells with the diploid number of chromosomes
contain an X and a Y chromosome (XY pattern), whereas female
cells contain two X chromosomes (XX pattern). As a conse-
quence of meiosis during gametogenesis, each normal ovum con-
tains a single X chromosome, but half of the normal sperm
contain an X chromosome and half contain a Y chromosome
(Figure 25–1). When a sperm containing a Y chromosome fertil-
izes an ovum, an XY pattern results and the zygote develops into a
genetic male.
When fertilization occurs with an X-containing
sperm, an XX pattern and a
genetic female
result. Cell division and
the chemical nature of chromosomes are discussed in Chapter 1.
Human Chromosomes
Human chromosomes can be studied in detail. Human cells are
grown in tissue culture; treated with the drug colchicine, which
arrests mitosis at the metaphase; exposed to a hypotonic solution
that makes the chromosomes swell and disperse; and then
“squashed” onto slides. Staining techniques make it possible to
identify the individual chromosomes and study them in detail
(Figure 25–2). There are 46 chromosomes: in males, 22 pairs of
autosomes plus an X chromosome and a Y chromosome; in fe-
males, 22 pairs of autosomes plus two X chromosomes. The indi-
vidual chromosomes are usually arranged in an arbitrary pattern
(karyotype).
The individual autosome pairs are identified by the
numbers 1–22 on the basis of their morphologic characteristics.Sex Chromatin
Soon after cell division has started during embryonic develop-
ment, one of the two X chromosomes of the somatic cells in
normal females becomes functionally inactive. In abnormal indi-
viduals with more than two X chromosomes, only one remains ac-
tive. The process that is normally responsible for inactivation is
initiated in an X-inactivation center in the chromosome, probably
via the transactivating factor CTCF (for CCCTC-binding factor),
which is also induced in gene imprinting. However, the details of
the inactivation process are still incompletely understood. The
choice of which X chromosome remains active is random, so nor-
mally one X chromosome remains active in approximately half of
the cells and the other X chromosome is active in the other half.
The selection persists through subsequent divisions of these cells,
and consequently some of the somatic cells in adult females con-
tain an active X chromosome of paternal origin and some contain
an active X chromosome of maternal origin.
In normal cells, the inactive X chromosome condenses and
can be seen in various types of cells, usually near the nuclear
membrane, as the
Barr body,
also called sex chromatin (Figure
25–3). Thus, there is a Barr body for each X chromosome in
excess of one in the cell. The inactive X chromosome is also visi-
ble as a small “drumstick” of chromatin projecting from the
nuclei of 1–15% of the polymorphonuclear leukocytes in
females but not in males (Figure 25–3).