Autoregulatory Control of Thyrotropin in Rabbits

Abstract

Studies were designed to determine whether an autoregulation system exists for TSH in the rabbit. For this purpose, a species-specific RIA for rabbit TSH that does not cross-react with human (h) TSH was developed. Hypothyroid animals were studied at varying time periods up to 3 months after either surgical thyroidectomy or propylthiouracil (PTU) treatment. Highly purified hTSH was injected iv at doses of 0 (saline control), 0.1, 0.3, 1,3, and 10 micrograms into unanesthetized rabbits bearing chronically implanted Silastic catheters. Blood samples were obtained at -30, 0, 10, 20, 30, 60, 120, 180, 240, and 300 min and 24 h. Doses between 0.3 and 10 micrograms hTSH produced a prompt fall (10 min) in rabbit TSH in hypothyroid rabbits studied 8-21 days after thyroidectomy. The minimum dose of hTSH that significantly suppressed rabbit TSH was 0.3 micrograms. This dose produced a peak value of hTSH in rabbit serum of 1.3 +/- 0.1 (+/- SEM) ng/ml 10 min after injection, which translates into a bioassay potency of 2.0 microU/ml (close to the physiological level in humans). A dose-response relationship existed between the hTSH dose injected and the duration and magnitude of suppression of rabbit TSH. This response to TSH was specific; 10 micrograms hTSH produced no change in endogenous rabbit serum LH and, conversely, 10 IU hLH produced no change in rabbit serum TSH. In contrast to these striking effects in acute hypothyroid animals, hTSH produced no detectable suppression of rabbit TSH in animals that were hypothyroid for 2-3 months. The sensitivity of the autoregulatory system to the suppressive effects of exogenous hTSH decreased with increasing duration of hypothyroidism; a time-response relationship existed. We conclude that: 1) a sensitive and specific autoregulatory control system for TSH exists in the rabbit; and 2) as the duration of hypothyroidism increases, the sensitivity of the autoregulatory system to the suppressive effects of endogenous TSH changes.

TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis

“…A similar constellation was described in patients with both familiar [39] and sporadic [40] activating TSH receptor mutations and in an infant born to a mother with Graves' disease [41]. This and the fact that ultrashort loop feedback control of thyrotropin secretion had been observed in rabbits [42, 43] led to the discovery of TSH receptors on folliculostellate cells of anterior pituitary lobe [44–46] and consecutive confirmation of a similar autocrine or paracrine effect in humans [47, 48]. This feedback loop might prevent excessively high TSH levels and also be a source of TSH pulsatility, as suggested by investigations based on fractal geometry [49].…”

Arginine Vasopressin as a Thyrotropin-Releasing Hormone

“…Stimulation of TSH release by AVP was modest in static incubation when compared with the peaks of release elicited by AVP perifusion. It is possible that accumulation ofTSH in static incubation media may exert a local feedback on TSH secretion at the pituitary level (23). The successive removal of released TSH during perifusion circumvents this problem and could account for the higher levels of secretion.…”

Thyroid stimulating hormone (TSH) autoregulation reduces variation in the TSH response to thyroid hormones

“…The existence of TSH autoregulation has been demonstrated by rabbit studies of hypothyroidism, using speciesspecific assay for rabbit TSH. These studies showed a fall in rabbit TSH levels when human TSH was injected [3]. After prolonged hypothyroidism this fall could not be demonstrated, indicating a possible loss of autoregulation in this circumstance.…”

“…After prolonged hypothyroidism this fall could not be demonstrated, indicating a possible loss of autoregulation in this circumstance. Autoregulation was found to be a sensitive system such that the suppression of rabbit TSH was of the same order as the rise in human TSH levels [3]. Autoregulation was active with changes to human TSH levels [3] corresponding to physiological levels.…”

“…Autoregulation is not unique to TSH physiology, as autoregulation of LH (Luteinising Hormone) [3], FSH (Follicle Stimulating Hormone) [4], prolactin [5] and ACTH (Adrenocorticotropic Hormone) secretion [6] has also been demonstrated.…”