Inter‐Relationships Between the Secretory Dynamics of Thyrotrophin‐Releasing Hormone, Thyrotrophin and Prolactin in Periovulatory Mares: Effect of Hypothyroidism

Abstract

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.

Role of Prolactin in the Gonadotroph Responsiveness to Gonadotrophin‐Releasing Hormone During the Equine Annual Reproductive Cycle

“…No direct inhibitory effects of endogenous or exogenous PRL on basal or GnRH‐induced LH release were detected. This corroborates previous findings in sheep where the same dose of rPRL was employed (14, 23, 34), indicating that hypersecretion of PRL alone is unlikely to affect the pituitary gonadotrophic axis in either species. TRH is known to stimulate PRL release in vivo and in vitro (14, 23, 34) and, in the present study, treatment with TRH evoked a three‐fold increase in PRL concentrations in both BS and NBS cultures.…”

Prolactin in the Horse: Historical Perspective, Actions and Reactions, and Its Role in Reproduction

“…Challenge with 10 mg of TRH resulted in a greatly enhanced TSH response in PTU-fed stallions but no alteration in the prolactin response. Similarly, Alexander et al [42] used pituitary venous blood sampling to assess prolactin and TSH secretion in periovulatory mares, half of which were previously made hypothyroid by PTU feeding. Their conclusion was that TRH is not a major factor controlling minute-to-minute fluctuations in either TSH or prolactin secretion.…”

Prolonged stimulation with thyrotropin-releasing hormone and pituitary adenylate cyclase-activating polypeptide desensitize their receptor functions in prolactin-producing GH3 cells

“…Similar to the GnRH receptor, TRHR is also desensitized by continuous exposure to its agonist. Indeed, TRH was found to be secreted in an irregular episodic pattern in mares (Alexander et al, 2004); and alterations in the pattern of prolactin release have been observed during the estrous cycle and lactation (Saunders et al, 1976). Changes in the pulsatility of TSH secretion have also been observed in hypothyroid humans (Greenspan et al, 1986).…”