When you put a mare on progesterone/estradiol, the addition of the estradiol inhibits follicular development in the majority
of mares. With the use of progestin/estradiol combination, progesterone prolongs the luteal phase; estradiol inhibits follicular
growth. With the addition of estradiol, you get a more significant negative feedback, and consequently, estrus synchronization,
due to both the progesterone and estrogen feedback, which inhibits FSH and LH. There is a more profound negative feedback
on FSH and LH than with progestin alone, which affects the onset transition of mares in the springtime. You have greater inhibition
of FSH and LH and a greater potential that LH will rise to initiate ovulation.
"One of the tricks we do with progesterone/estradiol treatment is to essentially block the release of LH and allow it to be
built up to a level so that once we do remove progestins/estradiol, there is enough of an LH-surge to stimulate ovulation,"
Brendemuehl says. "That is part and parcel to the mechanism action of how the progesterone/estradiol therapy works."
In a study at Colorado State, Burns investigated the use of a single-injection, 10-day progesterone versus a placebo control.
They looked at the average number of days from the first day the mare came into heat (with a 35-mm follicle) until ovulation,
with or without treatment. The difference was quite significant. The untreated mares took 19 days from the time they had a
breedable follicle until they ovulated. With treatment, it only took six days. With progesterone, there is not a prolonged heat and estrous cycle until ovulation.
"Those things really cause the average vet in the field, owners, and those shipping semen a lot of problems," Burns says.
Human chorionic gonadotropin
HCG is approved and licensed for use in veterinary practice for inducing ovulation in mares. For several years, hCG has been
used effectively in inducing ovulation in mares that are in behavioral estrus with a follicle of 35 mm or greater. HCG, having
LH biologic activity, is most effective given to mares that have not received it previously, presumed due to its antigenic
properties. It is therefore usually limited to being given during one or two estrous cycles in a given breeding season.
Whether GnRH or deslorelin (a GnRH analog) an injection in early spring will produce a nice surge of FSH, but you'll see almost
no LH release, as with other therapies because the pituitary does not contain sufficient LH early in the spring. Use of deslorelin
produces a hastening of ovulation in mares with preovulatory follicles greater than 30 mm. Johnson et al 2002 demonstrated
that mares induced to ovulate with deslorelin experienced suppressed gonadotropin (LH and FSH) secretion for several days
and desensitization to exogenous GnRH for at least seven days post-ovulation. A deslorelin implant produced an initial ovulation
two days sooner than untreated mares; their LH and FSH increased initially after implant but decreased thereafter. Though
plasma LH and FSH increased immediately following deslorelin administration, they both declined for several days thereafter.
Deslorelin also produced a prolonged inter-ovulatory period, between the initial ovulation and the subsequent one.
The dopamine antagonists probably work via their positive influence on prolactin, though additional research would be of interest
to thoroughly define their mode of action. Domperidone and sulpiride increase prolactin secretion indirectly, by blocking
the action of dopamine, whose action is to decrease the secretion of prolactin by the pituitary gland.
"I have used dopamine antagonists typically with a mare that is presented the first of February that hasn't been under lights,
so we don't have the luxury of waiting 45-60 days for her to respond to photoperiod stimulation," Brendemuehl says. "In some
of those mares in good body condition, we have had some success in putting those mares on a course of dopamine antagonist
therapy of domperidone or sulpiride, and having them respond positively in terms of follicular development and to start cycling
In work done at Colorado State and Cornell, use of the dopamine antagonists, domperidone and sulpiride, did not seem to promote
ovulation in mares during periods of severe cold weather.
"It probably has to do with the influence of the cold on thermoregulatory mechanisms, thyroid hormone function as it contributes
to ovarian hormone function, and probably even more so to what is going on in the hypothalamus, the pituitary and the influence
of corticosteroids," Brendemuehl says.