Pulsatile TSH Secretion during 48-Hour Continuous TRH Infusions

Abstract

Thyroid-stimulating hormone (TSH), like other anterior pituitary hormones, is normally secreted in a series of pulses over 24 h. However, the factors that control TSH pulse generation are unknown. We investigated the potential role of thyrotropin-releasing hormone (TRH) in TSH pulse generation by measuring TSH pulses during constant TRH infusions. Two groups of subjects were studied: five healthy subjects and five subjects with treated primary hypothyroidism and normal TSH levels. Each subject underwent four separate studies: (1) TSH levels were measured every 15 min over 24 h (baseline study). (2) TSH levels were measured every 15 min over 48 h during TRH infusions at 0.1 microgram/min (low dose TRH study). (3) TSH levels were measured every 15 min over 48 h during TRH infusion at 0.5 microgram/min (medium dose TRH study). (4) TSH levels were measured every 15 min over 48 h during TRH infusions at 1.0 microgram/min (high dose TRH study). TSH pulses were located by cluster analysis. We found that constant TRH infusions at any of the doses utilized did not alter TSH pulse frequency in normal or treated hypothyroid subjects, although pulse amplitude increased. Normal subjects had lower TSH pulse amplitude than treated hypothyroid subjects at all TRH doses, perhaps due to slightly higher serum T3 levels. This suggests that, at least acutely, pulsatile input of TRH to the pituitary gland does not determine pulsatile TSH release. However, TRH may modulate TSH pulse amplitude.

Intra-pituitary administration revisited: Development of a novel in vivo approach to investigate the ovine hypophysis

“…Our finding that TRH-induced prolactin secretion is sustained is consistent with studies administering TRH systemically to goats (Hashizume et al, 2009) and sheep (Robinson et al, 1996). Taken with other studies (Hartnell et al, 1987; Robinson et al, 1996; Samuels et al, 1993), this suggests that the prolactin response to TRH may not desensitize, which is in contrast to some other neurohormone/G protein coupled receptor systems (e.g. the ACTH response to CRF (Evans et al, 1988)).…”

“…In agreement with previous studies in the cow (Johke, 1978) and mare (Thompson et al, 1986), the amount of prolactin secreted in response to TRH was seasonally dependent in the ewe (lowest in Winter, highest in Spring/Summer), although the relative increase, compared to baseline, did not change with season. Although difficult to compare to other studies, it is noteworthy that the rate of intra-pituitary TRH infusion we used (17ng/μl/min) was ~30 fold lower than that used during iv infusion in sheep (Robinson et al, 1996; Taylor et al, 1986) and humans (Samuels et al, 1993). In the mare, a 5μg iv TRH injection was insufficient to stimulate prolactin secretion (Johnson, 1986).…”

Central Hypothyroidism in Children

“…TRH is also secreted in a pulsatile manner in the hypothalamus [25]; however, it seems that TRH only modulates the amplitude of TSH pulses, but not their frequency [26], suggesting a pituitary component is also active in the TSH pulse generator. Indeed, the pulsatile secretory profile of TSH is shown to be maintained in pituitaries experimentally 'disconnected' from the hypothalamus in animal models [27].…”

Extensions, Validation, and Clinical Applications of a Feedback Control System Simulator of the Hypothalamo-Pituitary-Thyroid Axis

“…We did assess several bioequivalence and replacement hormone 1 Biocybernetics Laboratory, Departments of Computer Science, Medicine, and Biomedical Engineering, UCLA, Los Angeles, California. 2 Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Sciences Center University, Portland, Oregon.…”