Effects on the Pituitary-Thyroid Axis and Prolactin Secretion of Single and Repetitive Oral Doses of Thyrotropin-Releasing Hormone (TRH)

Rabello, Maria M.; Snyder, Peter J.; Utiger, Robert D.

doi:10.1210/jcem-39-3-571

Cited by 82 publications

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“…Several studies have examined the effect of age and sex on the hypothalamic-pituitary-thyrotrophs axis by analyzing the TSH response to TRH injection [1][2][3][4][5][6][7][8][9][10][12][13][14][15][16][17] or to inhibitors of peripheral T 3 production. 11 Although the results were conflicting, most studies showed a diminished TSH response in the elderly and in males.…”

Section: Discussionmentioning

confidence: 99%

“…Significantly lower TSH response to TRH in young males compared to young females was found in some studies, 8,13,14 but not in others. 6,7,10,15 On the other hand, significantly diminished TSH response to TRH was found in elderly males compared to elderly females. 16,17 A diminished TSH response to TRH could be due to: 1) decreased thyrotrophs capacity to secrete TSH (or decreased thyrotrophs sensitivity to TRH), and/or 2) increased sensitivity of the thyrotrophs to the negative feedback of circulating thyroid hormones.…”

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confidence: 99%

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Influence of Age and Sex in Modulating TSH Level in Primary Hypothyroidism

Hammami

Al-Saihati

Alahmari

1995

Annals of Saudi Medicine

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Previous studies addressing the interaction of age and sex with the function of the hypothalamic-pituitarythyrotrophs axis yielded conflicting results, due in part to inability to control for the effect of variable free thyroid hormone levels. We studied the effect of age and sex on TSH levels in patients with severe primary hypothyroidism who have essentially undetectable plasma thyroid hormone levels. The TSH levels were measured in 116 thyroid cancer patients four weeks after the withdrawal of thyroxine therapy in preparation for radioiodine scan/treatment. All patients had a TSH ≥30 mU/L (normal = 0.2-5) and a free T 4 <6 pmol/L (normal = 10-25). Thirty males and 86 females with a mean age (± SD) of 40 ± 16 (range 6-89 years) were studied on up to four hypothyroid episodes, with a total of 191 episodes. The TSH level during the first hypothyroid episode correlated significantly with the TSH level during subsequent episodes (first episode versus second episode, r = 0.7, P -0.0001; first versus third episode, r = 0.6, P = 0.03). There was a significant negative correlation between age and TSH level (r = -0.24, P = 0.0009) that persisted when only the first hypothyroid episode was considered (r = -0.23, P = 0.01), or when only males (r = -0.32, P = 0.02) or only females (r = -0.23, P = 0.005) were considered. Means of TSH levels in males and females were not significantly different (130 versus 114 mU/L, respectively; P = 0.28). We conclude that age but not sex may modulate the sensitivity/responsiveness of the hypothalamic-pituitary thyrotroph axis to primary hypothyroidism. Ann Saudi Med 1995;15(6):575-578. MM Hammami, B Al-Saihati, S Al-Ahmari, Influence of Age and Sex in Modulating TSH Level in Primary Hypothyroidism. 1995; 15(6): 575-578 An age-related diminution in thyrotrophs function has been found by most, but not all, investigators. In response to an injection of a bolus of thyrotropin-releasing hormone (TRH), a decrease in thyroid-stimulating hormone (TSH) release was shown in elderly males and females, 1-3 in elderly males, 4 in elderly females, 5 and in elderly males but not in elderly females. [6][7][8][9][10] Further, the expected increase in TSH level in response to the inhibition of T 4 deiodination by oral iopanoic acid was not observed in healthy elderly volunteers.11 However, TSH response to a four-hour infusion of TRH was similar in the elderly compared to young male volunteers, although there was a small but significant increase in basal TSH concentration in the elderly. 12The effect of sex on thyrotroph function is even more controversial. Significantly lower TSH response to TRH in young males compared to young females was found in some studies, 8,13,14 but not in others. 6,7,10,15 On the other hand, significantly diminished TSH response to TRH was found in elderly males compared to elderly females. 16,17 A diminished TSH response to TRH could be due to: 1) decreased thyrotrophs capacity to secrete TSH (or decreased thyrotrophs sensitivity to TRH), and/or 2) increased sensitivity of...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Influence of Age and Sex in Modulating TSH Level in Primary Hypothyroidism

Hammami

Al-Saihati

Alahmari

1995

Annals of Saudi Medicine

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“…Sephadex G-10 and G-25 columns, being separated from PIF (Dular et al 1974;Machlin et al 1974). Several authors reported that TRH has properties of PRF (Noel et al 1974;Rabello et al 1974;Refetoff et al 1974). But TRH is recently demonstrated to be an important physiologic regulator of prolactin secretion (Malarkey and Beck 1975).…”

Section: Discussionmentioning

confidence: 99%

Relationship between prolactin secretion and hypothalamic prolactin releasing factor in pregnant and puerperium rats.

Takahashi¹,

Saito²,

Wakai³

et al. 1976

Tohoku J. Exp. Med.

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The present study attempted to elucidate stimulatory factor(s) in the rat hypothalamus which controls prolactin secretion from the anterior pituitary.Rat serum prolactin was elevated so much in late pregnancy that we prepared the hypothalamic extract of late pregnant rats. Prolactin levels in serum and pituitary were determined by radioimmunoassay. After injection of this extract into a lactating rat 43-60 hr after delivery, the serum prolactin level was elevated significantly one to four hr later and the pitui tary prolactin level declined two hr later. On the other hand, the hypothalamic extract of normal female rats prepared in a similar manner inhibited prolactin secretion from the anterior pituitary in the lactating rat as described by other authors.These data indicate that the prolactin releasing factor may consist in the hypothalamus of late pregnant rat, and be predominant over the prolactin inhibiting factor during late pregnancy. Prolactin secretion was also investigated in lactating and non-lactating puerperium rats. Prolactin in serum and pituitary declined with days after delivery in non-lactating rats, but not in lactating rats. The presumed factor for such prolactin release in lactating rats is considered to be the prolactin releasing factor. prolactin; prolactin releasing factor; hy pothalamus; lactation and pregnancyThe predominantly inhibitory influence of the hypothalamus on prolactin secretion from the pituitary has been well established.The stimulatory factor, however, was recently reported.The participation of serotonergic neurons appears to be important in the neuronal events leading to this hypothalamic stimulation of prolactin release (Lu and Meites 1973;Krulich 1975). In addition, oral admin istration of 5-hydroxytryptophan, a precursor of serotonin, significantly increases plasma prolactin (Kato et al. 1974).Although evidence of the hypothalamic regulation of prolactin secretion is generally accepted, there has been no establishment of hypothalamic control during pregnancy when prolactin secretion increases. In the present study, the prolactin releasing factor (PRF) in the hypothalamus was investigated using late pregnant

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“…Repetitive intravenous and chronical oral TRH administration in euthyroid and hypothyroid individuals results in a decrease of serum TSH 1,4, 34, 38,62,75 and in euthyroids in an increase of thyroid hormones within the upper normal range 3, 34, 62 The TSH decrease following TRH administration was also observed in athyroid patients 75. The latter finding may be suggestive for down regulation of the TRH receptor of the thyrotrophs which is transient 62, or for a predominant stimulation of TSH release and a slower de novo synthesis of pituitary TSH 38.…”

Section: Trh and Thyrotropie Activitymentioning

confidence: 94%

TRH: Pathophysiologic and clinical implications

Pickardt

Scriba

1985

Acta neurochir

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SummaryThyrotropin releasing hormone is thought to be a tonic stimulator of the pituitary TSH secretion regulating the setpoint of the thyrotrophs to the suppressive effect of thyroid hormones. The peptide stimulates the release of normal and elevated prolactin. ACTH and GH may increase in response to exogenous TRH in pituitary ACTH and GH hypersecretion syndromes and in some extrapituitary diseases.The pathophysiological implications of extrahypothalamic TRH in humans are essentially unknown.The TSH response to TRH is nowadays widely used as a diganostic amplifier in thyroid diseases being suppressed in borderline and overt hyperthyroid states and increased in primary thyroid failure. In hypothyroid states of hypothalamic origin, TSH increases in response to exogenous TRH often with a delayed and/or exaggerated time course.But in patients with pituitary tumors and suprasellar extension TSH may also respond to TRH despite secondary hypothyroidism. This TSH increase may indicate a suprasellar cause for the secondary hypothyroidism, probably due to portal vessel occlusion. The TSH released in these cases is shown to be biologically inactive.Keywords: TRH; diagnostic significance; hypothalamic diseases; pituitary failure. TRH, initially detected and synthesized as the hypothalamic hormone that controls the thyrotrophic activity was found to stimulate the prolactin release in vivo and in vitro 43, 45, 63, 72, 77 Moreover, TRH has been shown to be widely distributed over the central nervous system36, 3v, 44, 71, where it is believed to have neurotransmitter functions besides the hypophysiotropic effects.TRH has been detected in the upper gastrointestinal tract 14, where its endogenous functions are unknown. Exogenous TRH inhibits the pentagastrin stimulated gastric secretion 12 and by some degree the glucagon and pancreatic polypeptide release after insulin induced hypoglycemia 13. TRH and Thyrotropie ActivityExperimental and pathological disruption of the hypothalamic supply of the pituitary with TRH results in decreased thyroid function 47, called secondary hypothyroidism. TRH antibodies induce impairment of thyroid function with some effects on the prolactin secretion as well 28, 32, 39, 76. But until now, there are no consistent data on the physiological hypothalamopituitary relationship in humans. This is due to the fact that serum and urinary TRH is mainly derived from extrahypothalamic sources 46. In experimental hypoand hyperthyroidism the hypothalamic content of TRH does not change 52 arguing against a feedback inhibition between TRH and TSH. There are few studies reporting a decrease of TRH in hyper-and an increase in hypothyroidism with marked differences in the reported normal levels 29, 50. Most authors postulate today that TRH is a tonic stimulator of the TSH secretion, modulating the set point of the thyrotrophs to the suppressive effect of thyroid hormones 47.TSH responses to TRH are modulated by estrogens in females and in males 2o. This modulation is due to increasing binding sites of pituitary cell...

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Effects on the Pituitary-Thyroid Axis and Prolactin Secretion of Single and Repetitive Oral Doses of Thyrotropin-Releasing Hormone (TRH)

Cited by 82 publications

References 0 publications

Influence of Age and Sex in Modulating TSH Level in Primary Hypothyroidism

Influence of Age and Sex in Modulating TSH Level in Primary Hypothyroidism

Relationship between prolactin secretion and hypothalamic prolactin releasing factor in pregnant and puerperium rats.

TRH: Pathophysiologic and clinical implications

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