The pituitary-gonadal axis in healthy female dogs and bitches with gynecological disorders

Abstract

The pituitary gland produces and secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in a pulsatile fashion, induced by pulses of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Different cells in the ovary are capable of secreting estradiol, testosterone and progesterone, in response to LH and FSH. The ovarian hormones exhibit a feedback mechanism influencing the secretion of LH and FSH. The estrous cycle of the bitch is prevented most commonly by ovariectomy (OVX). Despite some potential side effects, most dog owners consider the procedure to be the method of choice for estrus prevention. The certainty of whether or not OVX has been performed in a bitch can be unclear when the animal has had previous owners or has been acquired from a shelter. Proving the presence of ovarian tissue in bitches is especially challenging during anestrus and consequently the use of GnRH in a provocation test of the pituitary-ovarian axis has been suggested. Therefore, the basal and GnRH-stimulated plasma concentrations of LH, FSH, estradiol, progesterone and testosterone were compared in anestrous and OVX bitches and data show that the mean basal plasma LH and FSH concentrations were significantly higher in OVX than anestrous bitches. Due to the pulsatile nature, overlap could occur in plasma LH concentration, but less likely in the plasma FSH concentration between both groups, indicating that a single measurement of the plasma FSH concentration is a reliable diagnostic tool to verify neuter status. GnRH administration resulted in a rise in the plasma estradiol concentration in both anoestrous and OVX bitches, while 120 min after GnRH administration no overlap existed between both groups. Differentiation between both groups with only a single basal plasma sample was best if the FSH to estradiol ratio was calculated. Also three important gynecological disorders in bitches were investigated. Remnant ovarian tissue (ROT) is due to incomplete surgical removal of one or both ovaries and can be very challenging to diagnose. Bitches with ROT had significantly higher basal plasma LH concentrations than anoestrous bitches and the concentration was higher in bitches in which estrus symptoms appeared for the first time more than 3 years after incomplete OVX. The basal plasma estradiol concentration was detectable in 17 of 18 bitches with ROT and in all 120 min after stimulation with GnRH. Granulosa cell tumors (GCTs) are the most frequently encountered hormone-producing ovarian tumors in middle-aged and older dogs, GCTs seem to appear more commonly in dogs with ROT. A high plasma LH concentration may play a role in the pathogenesis of GCTs. GCTs indeed seem to express functional gonadotropin receptors, since GnRH administration results in an increase of the plasma estradiol concentration. All dogs with a disorder in sexual development (DSD) described in this thesis had testicular tissue in their gonads and in three of them ovarian tissue was also present. The study revealed that the GnRH-stimulation test with measurement of plasma testosterone concentrations can be used to detect the presence of testicular tissue in dogs with DSD, while the plasma estradiol concentration is not informative about the presence or absence of ovarian tissue.