Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 21 Clinical Reproductive Endocrinology
O
OH
OH
2
3
1
A
4
11
19
10 9 8
B
5 6
7
OH
12 18
17 16
C 13 D
14
15
TESTOSTERONE
ESTRADIOL-17
ESTRONE
OH
in the strictest sense, and the expressions “ paracrine factor
” or “ local hormones ” have been used to describe these
substances. This is because prostaglandins are not secreted
from any particular gland and the biological half-life of
prostaglandins is usually extremely short, allowing, in most
cases, only a local action. Several different prostaglandins
are found in a number of types of mammalian tissues. One
prostaglandin released from the uterus, prostaglandin F 2 α
(PGF 2 α ), plays an important role in regulating reproductive
cycles in domestic species through the control of luteal
activity in nonpregnant animals and the initiation of delivery
in pregnant animals. The structures of prostaglandin
F 2 α and its main metabolite, 15-keto-13,14-dihydroprostaglandin
F 2 α , are presented in Figure 21-2 .
C . Hormone Receptors
O
O
PROGESTERONE
OH
OH
OH
OH
PGF 2
CH 3
C O
Because steroid hormones are fat soluble, they are able to
enter all cells of the body as the lipid cellular boundaries
present no barrier. Steroid hormone concentrations in plasma
are very low as compared to many compounds including their
important precursor, cholesterol. For example, plasma estrogens
in nonpregnant domestic animals range from as low
as 10 pmol/l to as high as 150 pmol/l. In this situation, most
cells within the body have very low concentrations of estrogen.
The specificity of tissue response occurs because cells
of tissues that have need of estrogen stimulation should have
receptors that enable those particular cells to concentrate the
H
O
OH
COOH
COOH
15-KETO-13,14-DIHYDRO-PGF 2
FIGURE 21-2 The number of sequence for the carbon atoms of the
steroid skeleton and lettering sequence for the four rings are shown for
testosterone. The structures of three other important sex steroid hormones,
estrone, estradiol-17 β , and progesterone, as well as the structure of
prostaglandin F 2 α and its blood plasma metabolite 15-keto-13,14-dihydroprostaglandin
F 2 α are also depicted.
hormone within the cell and, more important, to elicit particular
cellular responses. This explains the important generalization
that specific tissue response requires specific receptors to
be present within the cell, in this case for a particular steroid
hormone.
Binding of a hormone to a receptor in a target cell can
be considered to be the primary event and the hormone
receptor interaction will cause a measurable biological
response that differs for different hormones. Receptors
have a limited binding capacity (receptors are saturable
thus limiting number of hormone molecules that can enter
a target cell), they bind specific hormones (e.g., estrogen
receptors are specific for estrogenic compounds), and upon
binding a biological response will be created.
Steroid hormones enter cells by passive diffusion and
bind to receptors inside the cell. It is assumed that only
nonprotein bound or free hormone can enter target cells.
Traditionally, the steroid bound irreversible to the carrier protein
have been considered to be virtually biologically inactive
and only the minute quantity of free (nonprotein bound)
steroid can enter the cell. However, studies suggest that sex
steroids bound to the sex hormone-binding globulin can be
internalized and as the carrier is degraded by lysosomes,
the steroids are released to induce steroid-responsive genes
(Hammes et al. , 2005 ). When the steroid interacts with its
receptor, a steroid-receptor complex is formed. The hormonereceptor
complex is then activated and alters gene expression.
The target cell responds by increased RNA synthesis with
the transcription of specific mRNAs, which enters cytoplasm
and stimulates protein synthesis. The specific effect of steroid
hormones on target cells is an altered cell function related
to a change in the pattern of protein synthesis. In addition
to this classical genomic steroid action, rapid effects (within
minutes) of steroid have also been described (see Bramely
2003; Kelly and Wagner, 1999 ).
Protein hormones like GnRH, LH, and FSH do not enter
the target cell to exert their effects but interact with their
receptors, which are located on the plasma membranes of
the cell, s.c. G protein-coupled receptors. The binding of
the hormone to the cell surface receptor activates second
messenger(s), for example, cyclic AMP (3 , 5-AMP). The
second messenger(s) is the intracellular mediator of many
actions of LH and FSH in the ovary and the testis. The second
messenger(s) is thought to activate another intracellular
enzyme, protein kinase, which will influence the transport
of cholesterol into the mitochondrion and the conversion of
cholesterol to pregnenolone, which is the rate-limiting step
in the biosynthetic pathway for the steroids that play a significant
role in reproductive processes.
D . Local Conversion of Steroids in Target
Tissues
The effects of steroid hormones on cells can be accentuated
or modulated by the conversion of the entering hormone