Doses Of Thyrotropin-releasing Hormone Research Articles

Total thyroxine and thyroid-stimulating hormone responses of healthy cats to different doses of thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) stimulation can be used as a test of thyroid function and pituitary thyrotropin (thyroid-stimulating hormone, TSH) reserve, but optimal stimulation testing protocols in cats are unreported. We randomly divided 6 healthy young adult cats into 3 groups of 2 and administered 3 different intravenous doses of TRH (0.01, 0.05, 0.1 mg/kg) at weekly intervals in our crossover study. Serum TSH and thyroxine (T4) concentrations were measured using chemiluminescent immunoassay before, and at 30 and 60 min after, TRH administration. All cats were monitored for 4 h post-TRH administration for side effects. All 3 TRH doses induced significant TSH (0.01 mg/kg, p = 0.001; 0.05 mg/kg, p = 0.002; 0.1 mg/kg, p = 0.006) and total T4 (0.01 mg/kg, p = 0.008; 0.05 mg/kg, p = 0.006; 0.1 mg/kg, p = 0.001) responses. Lower TRH doses (0.01 and 0.05 mg/kg) caused fewer side effects (1 of 6 cats) than did the highest dose (3 of 6 cats), and may be safer in cats than the previously reported higher dose (0.1 mg/kg) of TRH. Our results do not support the use of maropitant to prevent side effects of a TRH stimulation test in cats.

Dorsal periaqueductal gray matter-evoked panic-like behaviors are markedly inhibited by a low peripheral dose of thyrotropin releasing hormone

Stimulation of the dorsal periaqueductal gray matter (DPAG) produces defensive behaviors which are reminiscent of panic attacks. Recent evidence from our laboratory showed that DPAG-evoked defensive behaviors are markedly attenuated in short-term methimazole-induced hypothyroidism. It is not clear, however, whether these effects were due to an increase in thyrotropin releasing hormone (TRH), a decrease in thyroid hormones or to the overall effects of hypothyroidism. Accordingly, here we examined whether the peripheral injection of TRH has any effect either on the panic-like behaviors induced by electrical stimulation of DPAG or anxiety-like behaviors of rats exposed to the elevated plus-maze (EPM). Rats whose stimulation of DPAG produced flight responses (galloping or jumping) with intensities below 60 microA were injected with 1 microg/kg TRH (i.p.) and stimulated 10min after that. The day after, rats were treated with saline and subjected to the same stimulation procedure. Threshold curves were fitted through the logistic model and compared by likelihood-ratio chi(2) tests. TRH and saline effects on EPM performance were appraised in separate groups. Compared to saline-sessions, TRH-injected rats presented thresholds significantly higher for immobility (40%), trotting (33%), galloping (34%), jumping (39%) and exophthalmus (43%). In contrast, TRH had no effects on EPM arm exploration. TRH selective inhibition of DPAG-evoked defensive behaviors adds new evidence that panic attacks may be attenuated by increased levels of this hormone in hypothyroidism.

Thyrotropin-releasing hormone (TRH) and vasopressin and oxytocin release: in vitro as well as in vivo studies.

Rats euhydrated and dehydrated for two or four days were given intracerebroventricularly (i.c.v.) thyrotropin-releasing hormone (TRH) in a daily dose of 200 ng dissolved in 10 microliters of 0.9% sodium chloride.) A single dose of TRH administered to euhydrated animals was followed by a significant increase of the vasopressin content in the neurohypophysis and hypothalamus as well as of the hypothalamic oxytocin content. On the contrary, a single dose of TRH decreased the oxytocin content in the neurohypophysis. Under conditions of dehydration TRH distinctly restrained the decrease of vasopressin and oxytocin in the hypothalamus. In animals dehydrated for two or four days the decrease of oxytocin in the neurohypophysis, brought about by stimulation of osmoreceptors, was distinctly more marked under treatment with TRH. On the contrary, the depletion of neurohypophysial vasopressin was significantly less apparent under such conditions. 28 nmol/L TRH markedly increased vasopressin release but inhibited that of oxytocin from the neurointermediate lobes incubated in vitro both under basal conditions as well as during stimulation with excess (56 mmol) potassium.

Expression of thyrotropin-releasing hormone receptors in rat testis and their role in isolated Leydig cells

Thyrotropin-releasing hormone (TRH) was initially discovered as a neuropeptide synthesized in the hypothalamus. Receptors for this hormone include TRH-receptor-1 (TRH-R1) and -2 (TRH-R2). Previous studies have shown that TRH-R1 and TRH-R2 are localized exclusively in adult Leydig cells (ALCs). We have investigated TRH-R1 and TRH-R2 expression in the testes of postnatal 8-, 14-, 21- 35-, 60-, and 90-day-old rats and in ethane dimethane sulfonate (EDS)-treated adult rats by using Western blotting, immunohistochemistry, and immunofluorescence. The effects of TRH on testosterone secretion of primary cultured ALCs from 90-day-old rats and DNA synthesis in Leydig cells from 21-day-old rats have also been examined. Western blotting and immunohistochemistry demonstrated that TRH-R1 and TRH-R2 were expressed in fetal Leydig cells (in 8-day-old rats) and in all stages of adult-type Leydig cells during development. Immunofluorescence double-staining revealed that newly regenerated Leydig cells in post-EDS 21-day rats expressed TRH-R1 and TRH-R2 on their first reappearance. Incubation with various doses of TRH affected testosterone secretion of primary cultured ALCs. Low concentrations of TRH (0.001, 0.01, and 0.1 ng/ml) inhibited basal and human chorionic gonadotrophin (hCG)-stimulated testosterone secretion of isolated ALCs, whereas relatively high doses of TRH (1 and 10 ng/ml) increased hCG-stimulated testosterone secretion. As detected by a 5-bromo-2'-deoxyuridine incorporation test, the DNA synthesis of Leydig cells from 21-day-old rats was promoted by low TRH concentrations. Thus, we have clarified the effect of TRH on testicular function: TRH might regulate the development of Leydig cells before maturation and the secretion of testosterone after maturation.

Central Thyrotropin-Releasing Hormone Infusion Opposes Cardiovascular and Metabolic Suppression during Caloric Restriction

Inhibition of hypothalamic thyrotropin-releasing hormone (TRH) neuronal activity is a well-established adaptation to caloric restriction (CR) that suppresses pituitary secretion of thyroid-stimulating hormone, but may also participate in modulation of autonomic function. Thus, we hypothesized that decreased hypothalamic TRH activity contributes to CR-induced bradycardia and decreased metabolic rate. To test this hypothesis, male Sprague-Dawley rats were instrumented with telemetry devices for measurement of heart rate (HR) and blood pressure (BP) and a lateral intracerebroventricular (i.c.v.) guide cannula for central infusions. After recovery, rats were housed in metabolic chambers and given either ad libitum(ad-lib) or CR treatments for 7 days; half of each diet group was then given continuous i.c.v. infusions of TRH (25 nmol/h) or saline (0.25 µl/h) for 7 days via osmotic pump. This dose of TRH did not significantly alter peripheral free T₄ levels. In ad-lib rats, TRH infusion produced small reductions in food intake and small increases in HR and BP over saline-infused controls. In CR rats, TRH infusion resulted in an increase in HR and also energy expenditure over saline-infused controls. These results support the hypothesis that suppression of central TRH activity contributes to the homeostatic suppression of energy expenditure and HR observed during CR.

Thyrotropin-Releasing Hormone as a Mediator of the Central Autonomic Pathway Controlling Ovarian Function

We studied the effect of thyrotropin-releasing hormone (TRH) applied centrally on the sympathetic activity of the ovary in female rats. Intracerebroventricular (i.c.v.) administration of a dose of 25 ng/kg weight produced an increase in noradrenaline (NA) content at the ovary after 5 days of hormone administration. However, higher doses in a range up to 500 ng/kg weight decreased NA content at the ovary. At the celiac ganglia (where the cell bodies of sympathetic neurons projecting to the ovary originate) there was an accumulation of NA in spite of a decrease in tyrosine hydroxylase activity (T-OH). After cold exposure, opposite effects on T-OH activity and no effects on NA in ganglia and in ovary were obtained. Besides, i.v. injection of TRH only induced a decrease in ovarian NA. In contrast to the increase in T₃ plasma levels obtained after the cold-stress procedure, none of the i.c.v. doses of TRH used produced changes in T₃ plasma levels, strongly suggesting that the effect on sympathetic activity is mediated by a central effect of TRH acting as a putative activator of ovarian sympathetic nerves.

Panic-related responses to pentagastrin, flumazenil, and thyrotropin-releasing hormone in healthy volunteers

Thyrotropin-releasing hormone ( TRH) induces some somatic symptoms that resemble those of a panic attack, without being considered to be a laboratory panicogen in panic disorder (PD) patients. This study aimed to identify doses of TRH and the laboratory panicogens, pentagastrin and flumazenil, that would produce a similar intensity of panic-related somatic symptoms in healthy volunteers because comparison of the effects of these doses in PD patients could be used to test the hypothesis that these agents have specific panicogenic effects that are not explained solely by cognitively mediated reactions to somatic symptoms. Nine subjects were administered pentagastrin (0.2 micro g/kg) and TRH (600 or 1,200 micro g) in a double-blind, randomized order, within-subjects design. Fifteen subjects received pentagastrin (0.1 micro g/kg), TRH (600 or 1200 micro g) and flumazenil (2 mg) in a double-blind, randomized order within-subjects design. Although low dose pentagastrin (0.1 micro g/kg) induced comparable cardiorespiratory responses to those of TRH, it induced greater anxiety, suggesting that TRH would not be a credible comparator for pentagastrin in challenge studies in PD. However, TRH produced equal or greater symptom and physiological responses compared with flumazenil, suggesting that flumazenil may act as a panicogen in PD via a GABAergic mechanism rather than via a cognitively mediated response to somatic symptoms. This now requires confirmation in PD patients.

Multiple injections of thyrotropin releasing hormone fail to reverse learning and memory deficits in rats with lesions of the nucleus basalis of meynert

The learning and memory enhancing effects of thyrotropin releasing hormone (TRH) was examined in an animal model of Alzheimer's disease. Adult rats were prepared with either sham surgeries or cholinergic lesions of the nucleus basalis of Meynert (nbM). Subjects were injected (ip) with one of three doses of TRH (0, 5, 10 mg/kg) starting on the day of surgery and continuing once every other day for a total of four injections. Performance (four trials/day for 4 days, 30 m inter-trial interval) in a Morris water maze was assessed one week after the last TRH injection (i.e., 2 weeks postoperatively). Latency to find the hidden platform served as the dependent variable. Results indicated that damage to the nbM impaired task performance in that animals with nbM lesions generally required more time to find the platform and showed less trial-to-trial improvement. Treatment with TRH failed to reverse this lesion-induced deficit. These results suggest that multiple injections of TRH do not provide residual protection against the deleterious effects on learning and memory produced by cholinergic lesions of the basal forebrain. Other doses and administration parameters, however, need to be studied in order to determine the generalizability of these findings.

Inhibition of pudendal reflexes in spinal rats: Reassessing the role of serotonin

The effects of serotonin (5-HT) and thyrotropin-releasing hormone (TRH) on penile reflexes were investigated in intact and spinally transected male rats. Doses of intrathecal 5-HT (0.0, 1.13, 2.26, 11.3, 22.6, and 113.0 nmol), in a range previously shown to inhibit pudendal reflexes in anesthetized spinal preparations, prolonged the latency to the first penile erection in awake intact rats. However, these doses also provoked hyperreactivity and vocalization. Doses of intrathecal TRH (100 and 500 pmol) that effectively inhibited penile erection in intact animals were less effective in spinalized animals. Finally, a combination of subthreshold doses of TRH (100 pmol) and 5-HT (4.0 nmol) at a ratio known to affect other TRH/5-HT-mediated circuits significantly extended erection latency in animals with spinal transections. These data suggest that 5-HT and TRH are both involved in the inhibitory circuits regulating penile erection, either through corelease onto the same population of cells or through independent release onto different populations of neurons.

Intrathecal methiothepin and thyrotropin-releasing hormone effects on penile erection

Intrathecal thyrotropin-releasing hormone (TRH) potently inhibits penile erection at all doses (100, 500, 1000 or 5000 pmol) tested so far. Since the serotonin receptor antagonist methiothepin (MT) inhibits TRH responses in other systems, this study tested the hypothesis that MT-sensitive receptors mediate the effect of TRH on penile erection in rats. When compared to controls, the highest doses of IT TRH (0, 10 or 500 pmol) or MT (5 or 50 nmol) significantly altered penile reflex latency. When coadministered (50 nmol MT/500 pmol TRH), the effect of TRH was reversed, suggesting that the high dose of MT antagonized the inhibitory actions of TRH. The low dose of MT (5 nmol) did not block the 500 pmol TRH inhibition of reflex latency. These data further suggest that MT sensitive receptors are important in (1) mediating normal penile reflexes and (2) mediating the inhibitory response to TRH.

Response of the pituitary and thyroid to tropic hormones in Sprague-Dawley versus Fischer 344 male rats.

Modulation of endocrine function is frequently a confounding factor in the interpretation of chronic rodent toxicology studies. Of particular interest are agents that cause deviation of thyroid hormone homeostasis and result in thyroid cancer for rodents. An endocrine challenge test (ECT), commonly used to study endocrine organ health in human and veterinary medicine, quantifies the response of the thyroid to tropic hormones. This study compared the response of Fischer (F344) and Sprague-Dawley (SD) rats to a thyrotropin-releasing hormone (TRH) ECT and a thyroid-stimulating hormone (TSH) ECT and characterized the dose-response curve. TSH, thyroxine (T4), triiodothyronine (T3), and prolactin responses were characterized for several doses of TRH over a 4-h time period. Animals were equipped with intra-atrial cannulae and were free moving at all times during blood sampling. Both strains of rats responded to intravenous TRH by releasing TSH into their blood in a dose-responsive fashion. At doses of > or = 100 ng, TSH concentrations were increased by more than 2-fold at 2 min. Concentrations reached a maximum at 15 min for doses of 100 ng/100 g body weight (bw) to 5000 ng/100g bw. The effective dose 50 (ED50) of TRH (that dose causing release of half maximal TSH concentrations) was 61 ng in F344 rats and 78 ng in SD rats. The ED75 was 173 ng and 217 ng/100 g bw, respectively. The response of T4 and T3 after TRH ECT and TSH ECT was highly variable. F344 rats responded with an increase in levels of both hormones, starting at 60 min and continuing through 240 min. In SD rats, the presence of a thyroid hormone response (T4) was present, although that of T3 was not clear. These data provide essential information for design of toxicology studies focused on the effects of toxicants and drugs on the pituitary-thyroid axis.

Involvement of nicotinergic mechanisms in thyrotropin-releasing hormone-induced neurologic recovery after concussive head injury in the mouse

A behavioral study was performed in an attempt to understand the neuronal mechanisms involved in the thyrotropin-releasing hormone (TRH)-induced improvement of consciousness after concussive head injury in the mouse. Intravenous administration of TRH dose dependently shortened the duration of unconsciousness after concussion in the mouse (ED 50=3.2 mg/kg). The improvement of recovery evoked by TRH (3 mg/kg i.v.) after concussion was not affected by i.p. pretreatment with N-(2-chloroethyl)- N-ethyl-2-bromobenzylamine, α-methyl- para-tyrosine, p-chlorophenylalanine, scopolamine or methylscopolamine. However, mecamylamine or hexamethonium i.p. pretreatment completely inhibited the TRH-induced improvement of outcome in traumatic brain injury. The results imply that TRH-induced improvement of recovery after concussion is not associated with increased activity of monoaminergic neurons in the brain. These results suggest that the inhibitory effect of TRH upon unconsciousness after concussion in mice is mainly produced by activation of central cholinergic systems via nicotinic receptors whereas muscarinic receptors seem to be not implicated.

Gender-biased activity of the novel prolactin releasing peptides: comparison with thyrotropin releasing hormone reveals only pharmacologic effects.

The prolactin- (PRL) releasing activities of the newly described PRL-releasing peptides (PrRPs) were compared to that of thyrotropin-releasing hormone (TRH) in dispersed, rat anterior pituitary cell cultures. A dose-related stimulation of PRL release by TRH was observed in cells harvested from both intact male and random cycle female pituitary donors. The minimum effective dose of TRH ranged from 1 to 10 nM. Neither PrRP-20 nor PrRP-31 significantly altered PRL secretion in cells from male donors even at doses as high as 1 microM. In cells harvested from females, only the highest doses of PrRP-20 and PrRP-31 tested (0.1 and 1.0 microM) significantly stimulated PRL secretion. The PRL-releasing action of TRH was observed already at 15 min of incubation, whereas those of PrRP-20 and PrRP-31 appeared only after 1 and 2 h of incubation, and the magnitude of PRL release in the presence of 1 microM PrRPs was significantly less than that of a similar dose of TRH. These data do not suggest a physiologically relevant role for the PrRPs in the neuroendocrine regulation of PRL secretion in intact male and nonlactating, random-cycle female rats.

Controlled trial of prenatal Thyrotropin-Releasing Hormone (TRH) and Betamethasone (B) for prevention of Respiratory Distress Syndrome (RDS).• 965

The use of TRH in conjunction with corticosteroids to prevent RDS in preterm pregnancies remains controversial. We conducted a multicenter, double-blind, randomized, controlled trial of prenatal administration of TRH(400 mg iv in 50 ml NS, q 8 h × 4) or placebo (PLC, 50 ml NS iv at same times) in women with singleton pregnancies ≤ 32 weeks' gestational age (GA) with threatened preterm delivery. All women in the trial received B (12 mg im q 24 h × 2). Live-born neonates < 1.0 kg received Exosurf soon after birth, whereas those ≥ 1.0 kg only received Exosurf as rescue therapy. The primary outcome of the study was RDS. A total of 370 women entered the trial(TRH n=190, PLC n=180) and 85% of them received all doses of TRH or PLC. GA at entry were 29.0 ± 2.2 vs 28.2 ± 2.3 d (mean ± SD), respectively. No benefits of maternal use of TRH were seen in either all neonates in the study or in the subgroup delivered between 1-10 days from entry. Air leaks were more common in the TRH group (7.0% vs 1.9%, respectively, RR= 1.38 i1.20-2.09, 95% C.I.ý).Other maternal or neonatal complications were similar in both groups. These data do not support the use of TRH in conjunction with B to prevent RDS when there is widespread surfactant availability. Funded by FONDECYT grant 193-0854.Table

Response of the Fetal Pituitary-Thiroid Axis (FPTA) To different Doses of Thyrotropin-Releasing Hormone (Trh)

Response of the Fetal Pituitary-Thiroid Axis (FPTA) To different Doses of Thyrotropin-Releasing Hormone (Trh)

Differential effects of intrathecal thyrotropin-releasing hormone (TRH) on perineal reflexes in male rats

The effects of thyrotropin-releasing hormone (TRH) on the sexual and defecatory reflexes regulated by pudendal motoneurons were investigated. Intrathecal TRH (10 μl volume; 0.0, 0.01, 1.0, or 100 μM concentration) at lumbosacral spinal segments (L4-S1) in acute preparations produced a dose-dependent increase in external anal sphincter (EAS), but not bulbospongiosus (BS), electromyographic (EMG) activity. Intraspinal (L6) injection of 100 μM TRH (1 μl/micropipette), significantly increased EAS EMG activity in acute preparations. Electromyographic activity of the BS muscle was unchanged. All doses of intrathecal TRH (10 μl volume; 0, 10, 50, 100, or 500 μM concentration) in awake animals significantly reduced the proportion of responders to a penile reflex test. Subsequently, all measures of penile reflexes were significantly reduced. Glans tumescence and defecation bouts before or during penile reflex testing were unaffected by intrathecal TRH as were indices of behavioral and motor hyper-reactivity analogous to that produced by serotonin. These data indicate that pudendal motoneurons, in the dorsomedial nucleus, are differentially regulated by neuropeptides present in the lumbosacral spinal cord.

Characterization of the calcium response to thyrotropin-releasing hormone in lactotrophs and GH cells

Thyrotropin-releasing hormone (TRH) acts via a G-protein-coupled receptor on lactotrophs to increase the intracellular free calcium ion concentration, [Ca 2+] i. The [Ca 2+] i response depends on both TRH concentration and the duration of TRH exposure. An initial, short-lived [Ca 2+] i spike results from release of Ca 2+ from intracellular stores, whereas a later sustained [Ca 2+] i increase, often characterized by [Ca 2+] i oscillations, results from an influx of extracellular Ca 2+ through both voltage-gated and non-voltage-gated, store-operated Ca 2+ channels. The initial spike phase predominates at high doses of TRH, whereas the plateau phase predominates at low doses. The mechanisms underlying the complex [Ca 2+] i response to TRH are discussed.

Thyrotropin-releasing hormone (TRH) and CNS regulation of anorectal motility in the rat

The effect of thyrotropin-releasing hormone (TRH) upon anorectal motility was investigated in acute male rat preparations. Micromolar doses of TRH were intrathecally (i.t.) infused at the L6 spinal level at a rate of 1 μl/min over 8 min. TRH infusions in 1.0–1000 μM concentrations elicited biphasic, dose-dependent anorectal contractions as measured by a rectal manometer. The 100 μM dose yielded the most significant increase in contractions over the greatest period of time. Atropine, administered as a pretreatment (100 μg s.c.), blocked contractions normally produced by i.t. infusion of TRH (1000 μM). Intravenous infusions of atropine (10 μg) through a jugular catheter immediately blocked anorectal contractions produced by i.t. infusion of 100 μM TRH. Sectioning of the hypogastric nerve, which supplies sympathetic innervation to the colon and internal anal sphincter, did not significantly affect contractions induced by 100 μM TRH applied intrathecally. Disruption of the major pelvic ganglion fibers, however, completely abolished the contractions induced by 100 μM TRH, either through the interruption of preganglionic parasympathetic fibers in the pelvic nerve, or by disrupting postganglionic fibers. These findings extend the role of TRH in the regulation of defecatory behaviors.

The cardiovascular and subjective effects of thyrotropin releasing hormone (TRH) and a stable analogue, dimethyl proline‐TRH, in healthy volunteers.

1. The cardiovascular effects of TRH 0.5 mg and 1 mg and a stable TRH analogue, dimethylproline-TRH (RX77368) 1 mg, infused intravenously over 1 min were assessed in healthy volunteers in two randomised, double-blind, placebo controlled crossover studies. 2. Both doses of TRH produced significant but transient increases in blood pressure (peak delta systolic: 0.5 mg = 9.2 mm Hg, 1.0 mg = 5.2 mm Hg; peak delta diastolic: 0.5 mg = 6.4 mm Hg, 1.0 mg = 5.4 mm Hg). 3. Beat-to-beat Finapres monitoring demonstrated a rapid onset of effects of RX77368 1 mg, with significant blood pressure effects by 45-60 s from the start of the infusion (delta systolic BP: 14.2 mm Hg, delta diastolic BP: 15.8 mm Hg and delta heart rate: 8.9 mm Hg at 60 s). 4. The pressor effects of RX77368 1 mg recorded by Dinamap (peak delta systolic: 14.3 mm Hg; peak delta diastolic: 11.8 mm Hg) were sustained, with diastolic pressure still elevated (delta diastolic: 8.2 mm Hg) at 60 min. Heart rate was more transiently elevated (peak delta heart rate: 9.0 beats min-1) during the first 6 min post infusion. 5. Mild apprehension was reported for the first 6 min after RX77368 1 mg, whereas paraesthesiae were noted after TRH. Otherwise both drugs were similar in the type (flushing, nausea, acid taste, urethral sensations) and duration of subjective effects.

Effects of thyrotropin releasing hormone on cardiac and extracardiac flows of appropriately grown and growth-retarded fetuses.

The objective of this study was to establish the effect of thyrotropin releasing hormone on the fetal circulation of appropriately grown and growth-retarded fetuses. Doppler recordings were performed immediately before and 15 min after maternal administration of 400 micrograms of thyrotropin releasing hormone in 14 women with appropriately grown and 19 with growth-retarded fetuses. Furthermore, in six women with growth-retarded fetuses, serial recordings were performed at 2-hourly intervals for 8 h until a second thyrotropin releasing hormone dose was administered. Velocity waveforms were recorded from the outflow tracts, inferior vena cava, umbilical artery, middle cerebral artery and descending aorta, and different Doppler indices calculated. In appropriately grown fetuses, thyrotropin releasing hormone induced a significant increase of peak systolic velocity values in the aorta and pulmonary artery and an increase of Doppler-estimated cardiac output. In growth-retarded fetuses, these changes were more evident and associated with a significant decrease in reverse flow in the inferior vena cava during atrial contraction. No changes were observed in fetal heart rate or in the other fetal vessels investigated. In the growth-retarded fetuses followed longitudinally, these changes were evident for the following 8 h and were potentiated by the second thyrotropin releasing hormone administration. In conclusion, thyrotropin releasing hormone induces significant hemodynamic effects on the fetal heart that may temporarily improve the impaired cardiac function of growth-retarded fetuses.