Review ArticleThyrotropin-Releasing Hormone: A Powerful Tripeptide With Diverse Effects in Horses
Introduction
Thyrotropin-releasing hormone (TRH) was the first hypothalamic factor to be isolated and chemically identified as a peptide hormone [1]. Two groups working independently in the United States [2], [3] reported in 1969 the structure to be a tripeptide: (pyro)Glu-His-Pro-NH2. The “pyro” prefix before the glutamic acid designator indicates that the amino end of the peptide forms a cyclic ring with the glutamic acid side chain carboxyl group and hence does not have a chemically active amino group like most peptides. This latter characteristic was the last to be deciphered and likely led to the extended period of time that it took for the scientists to finally match chemical structure of TRH to its biological activity [4], [5], [6].
Extensive research has been performed and reported on the biological activity of TRH in various species. The purpose of this review is to concentrate on what is specifically known for the horse regarding TRH activity and how that knowledge has been applied in research and clinical settings in the horse industry. For such a small molecule, TRH has an amazing diversity of effects on hypophyseal hormones in addition to the expected effects on thyroid-stimulating hormone (TSH).
Section snippets
TRH and TSH
The first reported use of TRH to stimulate TSH in equine research was by Thompson et al [7] in 1983. Daily treatment with 100 μg of TRH was used as a means to potentially stimulate plasma prolactin (PRL) concentrations in seasonally anovulatory mares. Plasma concentrations of TSH were measured around the first injection of TRH (or vehicle; administered intramuscularly) in treated and control mares, and TSH concentrations were found to increase in the first 30 minutes after TRH injection, peak
TRH and PRL
Perhaps the greatest amount of information regarding hormonal responses to TRH in horses is that concerning PRL. Johnson [23] and Johnson and Becker [24] were the first to describe the stimulatory effect of TRH on plasma PRL concentrations in horses. Johnson [23] reported that PRL response in mares to TRH was greater in June compared to January. He further demonstrated that increasing daily light exposure from 8 to 16 hours per day increased the PRL response to TRH, thus confirming the
TRH and Adrenocorticotropic Hormone
The first reported use of TRH in an equine clinical setting not involving the thyroid gland was by Beech and Garcia [19], who compared the cortisol responses of normal horses to those of horses with pituitary adenomas. As described by Beech [35] herself in her presentation on diagnosis of PPID in 2011, there was no readily available assay for the measurement of adrenocorticotropic hormone (ACTH) when she and Garcia reported their first study [19], thus cortisol response was used. With the
TRH and Alpha-Melanocyte-Stimulating Hormone (MSH)
Alpha-melanocyte-stimulating hormone (MSH) is a hormone that has gained notoriety due to its production and secretion by the intermediate lobe of the pituitary gland and its hypersecretion in horses with PPID. Accordingly, much of the literature on TRH and MSH overlaps with that for TRH and ACTH. Both ACTH and MSH are derived from the larger, preprohormone, pro-opiomelanocortin (POMC), which is found in both corticotropes in the distal lobe of the adenohypophysis as well as in melanotropes of
TRH and Growth Hormone
Growth hormone (GH) in horses, if similar to other species that have been well characterized, is under dual positive and negative control by the hypothalamus. Growth hormone–releasing hormone (GHRH) is believed to be the positive, trophic peptide affecting the somatotropes in the adenohypophysis, whereas GH-inhibiting hormone, more commonly referred to as somatostatin, is the inhibitory peptide. Supposedly, they are secreted by hypothalamic neurons in a somewhat temporally back-and-forth manner
TRH and Gonadotropins
Horses produce and secrete two distinct gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), from adenohypophyseal gonadotropes. Like in other species, horses have three types of gonadotropes [59]: those that contain secretory granules that stain for LH only, those that contain secretory granules that stain for FSH only, and those that contain secretory granules that stain for both gonadotropins. Except for the differential immunocytochemical staining for the
Summary and Conclusions
The hormones of the equine adenohypophyseal distal and intermediate lobes, their known hypothalamic control hormones, and the effects of TRH and other stimuli on their secretion are presented in Table 1. Four of the six known cell types are affected positively by TRH administration, and a fifth, the somatotropes, are affected negatively. The gonadotrope is the only cell type not affected by TRH, which in a way indicates that the other stimulatory effects are not just casual interactions of
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Cited by (3)
Plasma prolactin, thyroid-stimulating hormone, melanocyte-stimulating hormone, and adrenocorticotropin responses to thyrotropin-releasing hormone in mares treated with detomidine and butorphanol
2021, Domestic Animal EndocrinologyCitation Excerpt :Differentiation between these 2 possibilities could possibly be obtained from in vitro studies with isolated hypophyseal tissue. Given that prolactin- and MSH-secreting cells are both primarily regulated by tonic suppression by dopamine [19,20], albeit from different sets of neuronal pathways [19,20], it is interesting to note the differential effects of DET on the secretion of the 2 hormones after TRH. First, unstimulated (pre-TRH) MSH concentrations were increased by DET and DET/BUT, whereas prolactin concentrations were not affected in the first 10 min after treatment.
Melanocyte-Stimulating Hormone Response to Exercise, Twitching, Epinephrine Injection, Substance P Injection, and Prostaglandin-F <inf>2α</inf> Administration in Mares
2019, Journal of Equine Veterinary ScienceCitation Excerpt :Given that we have reported a greater MSH secretory response after sulpiride or TRH injection in insulin insensitive mares compared to sensitive mares [13], we compared insulin sensitivity estimates [19], which are relative consistent over time, from other trials to the MSH and ACTH responses in the five experiments herein and found basically no correlation overall. As mentioned in the Introduction, we previously suggested [9] that MSH was a good candidate for a stress-stimulated hormone in horses because of similarities with prolactin, GH, and ACTH in its regulation and factors that cause its release. Production and secretion of MSH in the intermediate lobe of the pituitary gland is tonically suppressed by dopaminergic input arising from the periventricular hypothalamic dopaminergic and tuberohypophyseal dopaminergic neural pathways [20,21].
Approved for publication by the Director of the Louisiana Agricultural Experiment Station as manuscript number 2017-230-31384.
Animal welfare/ethical statement: No animals were used in the generation of this review article.
Conflict of interest statement: The authors declare no conflicts of interest.