Inter-relationships between the secretory dynamics of thyrotrophin-releasing hormone, thyrotrophin and prolactin in periovulatory mares: effect of hypothyroidism.

We used our nonsurgical technique for collecting pituitary venous blood to relate the dynamics of thyrotrophin-releasing hormone (TRH) secretion to the secretion patterns of both prolactin and thyrotrophin in periovulatory mares, either euthyroid (n = 5) or made hypothyroid by treatment with propyl-thiouracil (n = 5). Pituitary venous blood was collected continuously and divided into 1-min aliquots for 4 h. To test the effect of dopamine on the relationship between secretion patterns, sulpiride, a selective D2 receptor antagonist, was given i.m. after 2 h of sampling. Thorough testing of the model and blood collection procedure revealed no sites of TRH loss. Hypothyroidism increased the mean secretion rates of TRH (P = 0.04) and thyrotrophin (P < 0.0001) but not prolactin. Sulpiride increased prolactin secretion rates in hypothyroid (P < 0.0001) and control (P = 0.007) mares, but did not alter TRH or thyrotrophin secretion rates. In both groups of mares, all three hormones were secreted episodically but not rhythmically. In both groups, the secretion pattern of TRH was almost always significantly related to that of thyrotrophin, as assessed by cross correlation and cross approximate entropy (ApEn) analysis. However, the degree of linear correlation was weak, with only 14% (hypothyroid) or 8% (controls) of the variation in thyrotrophin secretion rates attributable to TRH. Prolactin and TRH secretion patterns before sulpiride were coupled on cross ApEn analysis in both groups, and the minute-to-minute secretion rates of the two hormones were correlated in four hypothyroid and three euthyroid mares. Overall, the small, but significant, degree of association between TRH and prolactin was similar to that between TRH and thyrotrophin. In hypothyroid mares, sulpiride increased (P = 0.02) the synchrony between TRH and prolactin patterns. We conclude that in horses: (i) little TRH degradation occurs during passage through the pituitary or in blood after 1 h at 37 degrees C; (ii) TRH is not the major factor controlling minute-to-minute fluctuations in either thyrotrophin or prolactin; and (iii) reducing two strongly inhibitory inputs (i.e. dopamine and thyroid hormones) may magnify the stimulatory effect of TRH on prolactin secretion.

The effect of endotoxin administration on the secretory dynamics of oxytocin in follicular phase mares: relationship to stress axis hormones.

The primary aim of this study was to define the secretory dynamics of oxytocin and vasopressin in pituitary venous effluent from ambulatory horses during acute endotoxaemia, a stimulus that may release both hormones. Our secondary aim was to investigate the role of oxytocin in regulating adrenocorticotropic hormone (ACTH) secretion by comparing oxytocin, vasopressin, corticotropin-releasing hormone (CRH) and ACTH secretory profiles during endotoxaemia and by monitoring the ACTH response to oxytocin administration. Pituitary venous blood was collected nonsurgically continuously and divided into 1-min segments from eight follicular phase mares. Four mares were sampled for 30 min before and 3.5 h after receiving an i.v. infusion of bacterial endotoxin (TOX). Four control mares were sampled for 2.5 h without infusion of TOX. Another three follicular phase mares were given 5 U of oxytocin to replicate the peak response to TOX and pituitary blood collected every 1 min for 10 min before and 15 min after injection. Endotoxin raised the secretion rates of all hormones measured. All hormones were released episodically throughout the experiment, with TOX increasing the amplitude of peaks in each hormone. Peaks in oxytocin and vasopressin were coincident in each treated mare. Similarly, ACTH peaks were coincident with peaks of oxytocin and vasopressin in each treated mare, and with peaks of CRH in three mares. However, oxytocin administration did not affect ACTH secretion. We conclude that during endotoxaemia in horses: (i) oxytocin and vasopressin are secreted synchronously; (ii) oxytocin is unlikely to be acting as an ACTH secretagogue since inducing peak oxytocin concentrations observed during TOX does not raise ACTH; and therefore (iii) the close relationship between oxytocin and ACTH secretion is circumstantial and due to the fact that oxytocin secretion is concurrent with that of vasopressin, a proven ACTH secretagogue in horses.

Effectiveness of a two-dose regimen of prostaglandin administration in inducing luteolysis without adverse side effects in mares.

Our objectives were to determine whether repeated administration of prostaglandin F2alpha (PGF2alpha) to simulate the endogenous mode of secretion would be more effective than a single injection in inducing luteolysis and enable use of smaller doses less likely to cause adverse side effects. The main study comprised 43 dioestrous mares, who were given im. either a single 10 mg dose of natural PGF2alpha (n = 22) or 2 doses of 0.5 mg PGF2, 24 h apart (n = 21). The intensity of side effects was assessed in 8 dioestrous mares given 5, 1.5, 0.5 or 0 mg PGF2alpha in consecutive cycles. Two doses of 0.5 mg PGF2alpha 24 h apart caused lysis of the corpus luteum in all mares, whether this was determined from a fall in plasma progesterone concentrations or reproductive tract/behavioural changes; and when 10 mg PGF2, was given, the corpus luteum was lysed in 17 of 22 mares i.e. a lower proportion (P = 0.0485). A single dose of 0.5 mg PGF2a was no more effective than saline in inducing luteolysis.The intensity of side effects of PGF2alpha increased with dose. Although the 0.5 mg dose was no more likely than saline to cause sweating or muscle spasms, it raised plasma cortisol concentrations and prevented the decline in heart rate seen after saline. We conclude that a 2 dose regimen of administration increases the luteolytic efficacy of PGF2alpha and thereby provides a way to minimise adverse side effects.