Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

POLYPEPTIDE HORMONES
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Estrus (7–9 d): progesterone continues to rise in
response to the preovulatory LH surge that occurs
about the beginning of estrus. The bitch is receptive
to males. Ovulation occurs in response to the LH
surge and occurs around 42–54 h post-LH surge. It
has been shown, using ovarian ultrasonography, that
there is no significant difference in the time of ovulation
between the left and the right ovary. Ovulated
eggs are primary oocytes that cannot be penetrated
in vivo by the sperm until there is a complete resumption
of meiosis. Maturation, including the second
meiotic division, is complete after a further 54–75 h.
Ovulated oocytes are fertilizable for approximately
2 d but there may be breed differences.
Diestrus (57 d): progesterone is secreted throughout
diestrus.
Pregnancy (57–58 d from the first diestrus vaginal
smear, 65 d on average from the LH surge): progesterone
is secreted throughout pregnancy at levels
indistinguishable from a nonpregnant diestrus.
Anestrus (3–6 months): characterized by the absence
of circulating steroid hormones and a quiescent
endometrium.
The female cat (queen) is a seasonal breeder, requiring
increasing day length to begin cycling. The queen is an
induced ovulator, requiring mechanical stimulation of
the vagina and cervix or copulation to ovulate. However,
in specific cases (old queens, queens housed in catteries)
spontaneous ovulation may occur in a minority of
cases.
● Copulation is followed by an LH surge within
minutes and cessation of estrus within 48 h. Ovulation
occurs 30–50 h after copulation.
● Nonovulatory estrus cycles are normally followed
during the breeding season by return to estrus within
7–21 d.
● Ovulatory estrus cycles are followed by pregnancy
(63–68 d) or by nonpregnant diestrus (25–45 d),
both of which are characterized by high circulating
progesterone.
POLYPEPTIDE HORMONES
Endogenous polypeptides include GnRH, the gonadotropins,
oxytocin and prolactin.
Relevant physiology
The peptide hormones are constructed from amino acids
and are stored and secreted in response to specific triggers.
Circulating polypeptide hormones bind to membrane
receptors on target cells to activate adenyl cyclase
and, via a second messenger, cytoplasmic protein kinase,
to induce steroid synthesis and secretion.
Gonadotropin-releasing hormone (GnRH)
GnRH is a hypothalamic decapeptide. GnRH agonists
have one or two amino acid changes in the GnRH
chemical structure.
EXAMPLES
GnRH formulations include gonadorelin diacetate
tetrahydrate (hypothalamic decapeptide) and gonadorelin
HCl (hypothalamic decapeptide).
GnRH agonists such as fertirelin acetate and buserelin
often have increased GnRH receptor affinity. Several
synthetic analogs such as lutrelin, deslorelin and nafarelin
have recently been used experimentally for regulating the
estrous cycle in bitches. More than 700 GnRH agonists have
been synthesized.
Under normal conditions, GnRH or GnRH agonists are
short acting drugs. When they are administered as subcutaneous
implants they may be used as long-acting
devices.
Mechanism of action
GnRH stimulates a surge release of endogenous FSH
and LH from the anterior pituitary that acts to:
● cause follicular maturation, ovulation and
progesterone secretion in the bitch and queen
● promote testosterone secretion in the male dog
and cat.
GnRH agonists also stimulate, with different potencies,
production and release of gonadotropins from the pituitary.
Conversely, when used at sustained doses GnRH
agonists reversibly inhibit (after a short period of stimulation)
the gonadal axis by downregulating the anterior
pituitary GnRH receptors.
Clinical applications
In bitches
● GnRH causes release of LH, which may induce ovulation
in estrous bitches and will promote luteinization
of follicular cysts in bitches with functional
ovarian cysts.
● GnRH has been used experimentally to induce estrus
in anestrus bitches.
● Postponement of puberty.
In queens
● GnRH-mediated release of FSH and LH will allow
estrus induction in queens.
● GnRH will induce ovulation in queens.
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