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

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Chapter | 21 Clinical Reproductive Endocrinology
on reproductive function. It has also been shown that other
organs like the uterus and the hypothalamus, although they
may not fulfill the strict requirement of being defined as
endocrine glands, can synthesize and secrete hormones that
have a profound influence on reproductive function.
B . Chemical Classes of Reproductive
Hormones
1 . Peptide and Protein Hormones
a . Releasing Hormones
Several types of hormones are involved in the regulation of
reproduction. Releasing hormones are peptide hormones,
which are produced within the hypothalamus and transferred
via the hypothalamo-hypophyseal portal veins to the adenohypophysis,
where they regulate the synthesis or release
of adenohypophyseal hormones. Gonadotropin-releasing
hormone I (GnRH), a decapeptide with the sequence pGlu-
His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH 2 , regulates the
release of two important reproductive hormones, luteinizing
hormone (LH) and follicle-stimulating hormone (FSH). A
conserved second GnRH (GnRH-II) form exists in some
mammals but appears not to have importance for gonadotropin
release ( Millar, 2005 ). Thyrotropin-releasing hormone,
a tripeptide (pGlu-His-Pro-NH 2 ), which regulates the synthesis
and release of thyroid-stimulating hormone (TSH),
also causes the release of prolactin in several species.
GnRH is released in a pulsatile fashion, where the frequency
of peaks varies according to reproductive status
(see Clarke and Pompolo, 2005 ). Recently discovered neuropeptides
have shed some light on the central regulation
of GnRH release. Kisspeptin (or mestatin) and its receptor
(G protein-coupled receptor 54) are expressed in the
hypothalamus in close connection with GnRH-neurons.
Kisspeptin is regulated by sex steroids and can directly
activate GnRH neurons and induce GnRH secretion; thus it
may be an important regulator of the reproductive axis and
puberty ( Seminara, 2005 ). First discovered in birds ( Tsutsui
et al. , 2000 ), gonadotropin-inhibiting hormone (GnIH) has
also been demonstrated in mammals, where its hypothalamic
localization, association with steroid receptors, and inhibiting
effect on gonadotropin secretion suggest an important
role in the reproductive axis ( Kriegsfeld et al. , 2006 ).
b . Hypophyseal Hormones
Luteinizing hormone (LH) and follicle-stimulating hormone
(FSH) are glycoproteins containing 13% to 25% carbohydrate.
The molecular weight of LH in domestic animals
(bovine, ovine, porcine, equine) is about 30,000. Ovine
and equine FSH have molecular weights of about 32,000.
Prolactin is a protein with a molecular weight of approximately
23,000 (bovine, ovine, porcine). Luteinizing hormone
and FSH, as well as TSH, consist of two nonidentical
subunits designated α and β . Within a species, the α-subunit
is identical for these glycoprotein hormones, whereas the
β -subunit is unique for each hormone and determines the
biological activity. Individual subunits by themselves possess
little or no biological activity and are probably not released
into the circulatory system under normal physiological
conditions.
The cells of the adenohypophysis can be divided into
basophiles (affinity for basic stains) and acidophiles (affinity
for acid stains). Luteinizing hormone and FSH are produced
within basophilic cells; it has been demonstrated
that LH and FSH can be present within the same cell (the
gonadotrope) . Prolactin, on the other hand, has been localized
in acidophilic cells. Gonadotropes have G proteincoupled
GnRH-receptors on their surface, and the secretion
of LH and FSH during the ovarian cycle is controlled by
changes in the frequency of GnRH pulses. Except during
the preovulatory LH surge in the estrus cycle, there is a
clear difference in the patterns of FSH and LH secretion,
as measured in the peripheral circulation, and only LH is
released in a clear pulsatile manner reflecting GnRH secretion
(see Pawson and McNeilly, 2005 ).
c . Neurohypophyseal Hormones
The posterior pituitary is responsible for storage and release
of oxytocin, an important reproductive hormone, and antidiuretic
hormone (vasopressin). These two hormones are
synthesized primarily in the regions of the paraventricular
nucleus and supraoptic nucleus of the hypothalamus. The
hormones are transported to the posterior pituitary by axoplasmic
fluid. Release of these hormones occurs as a result
of stimulation of the nerve cell bodies in the nuclei. Oxytocin
is an octapeptide with a molecular weight of 1000.
d . Gonadal Activins and Inhibins
Activins and inhibins are structurally related proteins
belonging to the transforming growth-factor- β (TGF-β)
superfamily and have impact on the endocrine reproductive
axis. Inhibins and activins are made up of two peptide
chains. Inhibins form α-β dimers and activins β-β dimers.
There are two varieties of the β -unit (called A and B) producing
two forms of inhibin, inhibin A ( α-β A), and inhibin
B ( α-β B), and three forms of activin, activin A ( βA-βA),
activin B ( βB-β B), and activin C ( βA-β B). Activins and
inhibins secreted from the gonads act antagonistically on
the gonadotropes to regulate FSH release. In the female,
activins have several autocrine/paracrine functions in reproductive
tissues and ovary activin A has been indicated as an
endocrine stimulator of FSH release. In the male, inhibin is
produced by Sertoli cells and function as a negative feedback
regulator of pituitary FSH, probably in synergy with
testosterone. In most species (e.g., bull, boar, and stallion),
the dominant testicular form is inhibin B, whereas in the
ram, inhibin A appears to be the dominant inhibin of the
testicles of adult males ( McNeilly et al. , 2002 ).