In vitro TSH and PRL secretion from eutopic and heterotopic rat pituitaries: effects of hypothyroidism

Five adenohypophyses from donors of the same strain, age, and sex were transplanted under the renal capsule of young adult female rats. At least 3 wk later, enzymatically dispersed cells from eutopic or heterotopic adenohypophyses from the same rat were perifused in vitro in a small chamber. Thyrotropin (TSH) and prolactin (PRL) secretion per 10(6) cells were significantly less from heterotopic than from eutopic cells under all conditions. In cells from euthyroid animals, TRH induced TSH secretion only in the eutopic cells but induced PRL secretion in both eutopic and heterotopic cells. Hypothyroidism increased TRH-induced TSH secretion and content in the cell lysate in both eutopic and heterotopic cells but increased TRH-induced PRL secretion only in the eutopic cells. The increase in TSH secretion induced by hypothyroidism in the heterotopic cells was of borderline statistical significance. The inability of TRH to induce TSH secretion in heterotopic pituitary cells from euthyroid rats may be due to a lower set point for thyroid hormone inhibition of TSH secretion in the heterotopic thyrotrophs. Heterotopic pituitary TSH secretion is probably suppressed by the normal plasma thyroid hormone concentration maintained by the eutopic pituitary and may be stimulated by TRH only in the presence of a subnormal plasma thyroid hormone concentration.     

Immunocytochemical detection of effects of TRH and T4 on prolactin- and TSH-producing cells in the pituitary gland of Rana ridibunda

Effects of synthetic thyrotropin-releasing hormone (TRH) and various doses of thyroxin (T4) on prolactin (PRL)-producing cells and thyrotropic cells in the pituitary were investigated in adult male and female Rana ridibunda frogs. Animals were given 200 microg TRH once a week for 4 weeks and 0.2-0.5 mg T4 during 3 days per week for a period of 2 weeks by injections in the groin. PRL-producing cells and thyrotropic cells were identified with light microscopical and electron microscopical immunocytochemical methods, using rabbit anti-PRL and rabbit anti-thyroid stimulating hormone (TSH) as primary antibodies. TRH caused cytological changes in both cell types, which were consistent with increased synthesis and release of both PRL and TSH. Treatment with 0.5 mg T4 activated both cell types less than TRH treatment did, whereas 0.2 and 0.4 mg T4 caused inactivation of both cell types. In conclusion, mammalian TRH is effective on both types of frog pituitary cells. Our study suggests that T4 has a positive rather than a negative effect when concentrations above a certain threshold are given.     

Endocrine effects of the H2-receptor antagonists cimetidine and ranitidine

This paper reviews investigations on the endocrine effects of two H2-receptor antagonists, cimetidine and ranitidine. Cimetidine has hyperprolactinaemic properties and interferes with the peripheral activity of the sexual hormone (DHT) and probably with the pituitary LH secretion. A possible effect on TSH and thyroid hormone secretion or peripheral metabolism is suggested. Ranitidine seems to have no central or peripheral effects (after both acute and chronic administration) on sexual hormones. High doses (300 mg i.v. bolus) of the drug induce a significant increase in prolactin basal levels, whereas no effects follow oral administration. The effects on PRL are sex-related and less marked than those obtained with cimetidine. The chronic administration of this drug does not affect basal or TRH-stimulated PRL levels. No effects were apparent on TSH serum levels after either oral or i.v. acute administration, whereas lower basal and TRH-stimulated T4 values were registered after chronic treatment. On the basis of these results, a possible interference of ranitidine on iodothyronine metabolism can be suggested.     

Melatonin reduces the production and secretion of prolactin and growth hormone from rat pituitary cells in culture

A culture of clonal tumour cells from rat pituitary gland that secrete both prolactin and growth hormone were used to investigate whether the pineal hormone melatonin can act directly on the pituitary gland to control prolactin production. Melatonin inhibition of prolactin and growth hormone production was significant but mild. Concentrations of between 10(-8) M and 10(-6) M reduced both prolactin and growth hormone production and prolactin secretion by 10-50%. 17 beta-oestradiol (OE) and thyrotrophin-releasing hormone (TRH) stimulated prolactin production but had no significant effect on growth hormone production. Melatonin reduced the effects of both of these compounds. Both TRH and vasoactive intestinal peptide (VIP) stimulated secretion of prolactin, and TRH also of growth hormone. Melatonin reduced these effects significantly. TRH and VIP increased cAMP production two- and 12-fold, respectively. Melatonin had no effect on basal or stimulated cAMP production. The melatonin-induced changes in prolactin and growth hormone production and secretion seen here do not approach the magnitude of the fluctuations seen in plasma in vivo. It is concluded that while melatonin does have a direct effect on the lactotroph in the regulation of prolactin production, its main physiological target must be elsewhere.     

Effects of atrial natriuretic factor on anterior pituitary hormone secretion in normal man

Summary The effects of intravenous human atrial natriuretic factor ANF(99-126) administration on anterior pituitary hormone secretion have not been extensively investigated in humans. We repeatedly studied 10 healthy volunteers (5 female, 5 male, aged 28±2 years) on 2 occasions, 3 days apart. In randomized, single blind order, subjects received pretreatment with either placebo or intravenous ANF(99–126) (bolus 100 g/kg, 30-min infusion of 0.1 g/kg-min). Subsequently, on both occasions subjects received a combined intravenous bolus injection of pituitary releasing hormones (200 pg thyrotropin releasing hormone, 100 g gonadotropin releasing hormone, 50 g growth hormone releasing hormone and 100 g human adrenocorticotropin releasing hormone; Bissendorf, Hannover, FRG). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), thyrotropin (TSH), prolactin, ANF and cyclic guanosine monophosphate (GMP) were determined by radioimmunoassay. ANF(99–126) treatment induced a significant reduction in basal ACTH plasma concentrations and tended to decrease basal plasma cortisol. The TSH response to combined releasing hormone administration was significantly diminished after ANF(99-126) pretreatment. In women, the releasing hormone induced prolactin increase was reduced after ANF(99–126) pretreatment. With the present study design, ANF(99–126) did not alter the basal or releasing hormone stimulated plasma concentrations of cortisol, LH, FSH and GH. Releasing hormone administration did not affect ANF and cyclic GMP plasma levels. In humans, effects of natriuretic peptides on anterior pituitary hormone secretion may have to be considered with investigational or therapeutic administration of ANF analogues or agents interfering with the ANF metabolism.Abbreviations ANF(99–126) human atrial natriuretic factor - ACTH adrenocorticotropic hormone - LH luteinizing hormone - FSH follicle-stimulating hormone - GH growth hormone - TSH thyrotropin - PRL prolactin - cyclic GMP cyclic guanosine monophosphate - TRH thyrotropin releasing hormone - GnRH gonadotropin releasing hormone - GHRH growth hormone releasing hormone - CRH adrenocorticotropin releasing hormone     

Effect of diphenylhydantoin on hypothalamic-pituitary-thyroid function in the rat

Chronic diphenylhydantoin (DPH) administration (5 mg x 100 g body wt-1 x day-1) to the normal rat is associated with a decrease in the serum thyroxine (T4) and triiodothyronine (T3) concentrations without an appropriate rise in the serum thyrotropin (TSH) concentration, suggesting a possible direct effect of DPH on TSH secretion. To further study this possibility, DPH was administered chronically to thyroidectomized, hypothyroid rats. In the hypothyroid rats treated chronically with DPH, serum TSH did not increase, pituitary TSH content was significantly decreased, and the serum TSH response to thyrotropin-releasing hormone (TRH) was decreased compared to that of diluent-treated, hypothyroid rats. Hypothalamic TRH content was similar in DPH and diluent-treated rats. These findings suggest that DPH suppresses pituitary TSH secretion, probably as a thyroid hormone agonist. The effect of a single large dose of DPH (20 mg/100 g body wt) administered to thyroidectomized rats also decreased serum tSH but, in contrast to the findings in chronically treated rats, hypothalamic TRH and pituitary TSH content and the serum TSH responses to TRH were increased. These differences may be due to the acute inhibitory effect of a large dose of DPH on hypothalamic TRH release. Furthermore, because the effect of thyroid hormone on regulating pituitary TSH synthesis and release is dose and time dependent, the effect of DPH as a thyroid hormone agonist on pituitary TSH dynamics may also be variable.     

Transdifferentiation of pituitary thyrotrophs to lactothyrotrophs in primary hypothyroidism: case report

Primary hypothyroidism causes adenohypophysial hyperplasia via stimulation by hypothalamic thyrotropin-releasing hormone (TRH). The effect was long thought to simply result in thyroid-stimulating hormone (TSH) and prolactin (PRL) cell hyperplasia, an increase in TSH and PRL blood levels with resultant pituitary enlargement, often mimicking adenoma. Recently, it was shown that transformation of growth hormone (GH) cells into TSH cells takes place in both clinical and experimental primary hypothyroidism. Such shifts from one cell to another with a concomitant change in hormone production are termed "transdifferentiation" and involve the gradual acquisition of morphologic features of thyrotrophs ("somatothyrotrophs"). We recently encountered a unique case of pituitary hyperplasia in a 40-year-old female with primary hypothyroidism wherein increased TSH production was by way of PRL cell recruitment. The resultant "lactothyrotrophs" maintained TSH cell morphology (cellular elongation and prominence of PAS-positive lysosomes) but expressed immunoreactivity for both hormones. No co-expression of GH was noted nor was thyroidectomy cells seen. This form of transdifferentiation has not previously been described.     

The phorbol ester TPA induces hormone release and electrical activity in clonal rat pituitary cells

The phorbol ester TPA activates the protein kinase C in a similar way as 1,2-diacylglycerol. The effect of TPA on prolactin (PRL) secretion and electrical properties of rat pituitary cells in culture (GH4C1 cells) were compared with the effects of thyroliberin (TRH) on the corresponding parameters. The rate of hormone release was measured using a parafusion system optimized to give high time resolution. Samples for PRL measurements were taken every 4 s. The TRH evoked a biphasic PRL release, with a transient peak after about 30 s followed by a lower but sustained enhancement of the secretion. The TPA mimicked the late phase of the secretory response to TRH. The TPA analogue, 4 alpha-PDD, had no effect on the PRL release. The TRH also evoked biphasic membrane potential changes in the GH4C1 cells; the late phase consisting of membrane depolarisation associated with increased input resistance and enhanced firing of Ca2+ dependent action potentials. The TPA mimicked to a great extent these late phase effects of TRH, whereas the inactive analogue 4 alpha-PDD was ineffective. Continuous exposure to TPA masked the late phase of the electrophysiological response to TRH, suggesting that TPA and TRH share common mechanisms in their action on GH4C1 cells. We suggest that TRH enhances the electrical activity in these cells due to protein phosphorylation induced by diacylglycerol activation of protein kinase C, which in turn suppresses the membrane permeability to K+.     

Central galanin stimulates pituitary prolactin secretion in rats: possible involvement of hypothalamic vasoactive intestinal polypeptide

The effect of galanin, a newly identified neuropeptide, on pituitary prolactin (PRL) secretion was examined in the rat. Intracerebroventricular (i.c.v.) injection of all 5 doses of galanin (0.4, 1, 2, 5 and 10 micrograms/rat) raised plasma PRL levels in urethane-anesthetized rats. Galanin injection (2 micrograms/rat, i.c.v.) also increased plasma PRL levels in conscious rats. The intermediate dose of galanin (2 micrograms/rat, i.c.v.) produced a greater response in plasma PRL levels than either smaller or larger doses of galanin. Intravenous injection of galanin did not affect plasma PRL levels. Passive immunization with specific anti-vasoactive intestinal polypeptide (VIP) rabbit serum suppressed plasma PRL response to galanin (2 micrograms/rat, i.c.v.) in anesthetized rats. These findings indicate that central galanin has a stimulatory role in pituitary PRL secretion via the hypothalamus in the rat and that VIP may be involved in rat PRL release induced by galanin.     

Interaction between vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in stimulating the secretion of prolactin from rat anterior pituitary cells in vitro

Interaction between vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in regulating the secretion of prolactin (PRL) from the pituitary was investigated in the rat in vitro using two different methods: (1) short incubation of anterior pituitary cells and (2) superfusion of the pituitary cell column. PRL levels in the incubation medium were raised by addition of either VIP or PHI in concentrations of 10(-9) M to 10(-7) M in a dose-related manner. When both peptides were simultaneously added, additive stimulating effect on PRL release was obtained below the VIP concentration of 10(-7) M, in which no additive effect of PHI was revealed. PRL release from superfused rat pituitary cells was stimulated by 5-min pulses of VIP (10(-7) M), PHI (10(-7) M) and TRH (10(-8) M). Infusion of VIP for 200 min in the concentration of 0.3 x 10(-7) M resulted in an increase in basal release of PRL and blunted PRL release induced by not only VIP but also PHI stimulation, whereas PRL release induced by TRH was not affected. Infusion of PHI (0.3 x 10(-7) M, 0.7 x 10(-7) M and 10(-7) M) for 200 min also dose-relatedly suppressed PRL release induced by not only PHI but also VIP without any change in PRL release induced by TRH. These findings suggest that VIP and PHI may act through a common binding site on the pituitary lactotroph in the rat.     

Growth hormone and thyrotropin secretory profiles and provocative testing in aged rats

The impact of aging on both basal and induced GH and TSH secretion in male and female rats was investigated. Analysis of the individual GH secretory profiles in young (3-4 month) and old (19-20 month) rats indicated that sex-dependent patterns of GH secretion was preserved in old animals. However, we observed a reduction of individual GH peak amplitudes of 66% in old males and 53% in old females when compared to their respective young animals. Further, the GH response to an intravenous bolus of GH-releasing factor (GRF), morphine and clonidine was dramatically blunted or absent in old male and female animals. In contrast to GH, basal TSH secretion was elevated, while the TSH response to thyrotropin-releasing hormone (TRH) was not significantly affected in old animals of either sex. The present data provide evidence that reduced pituitary sensitivity to GRF may be a possible cause for reduced GH secretion in old animals. Further, the elevation in plasma TSH observed in old animals is not the result of an increased pituitary sensitivity to TRH.     

On the functional relationship between 45Ca2+ release and prolactin secretion in cultured rat pituitary tumour (GH3) cells

We have evaluated the role of cellular Ca2+ transport associated with stimulus-secretion coupling in prolactin (PRL) producing rat pituitary adenoma cells (GH3 cells). The action of different substances, known to modify PRL secretion, on release of 45Ca2+ from preloaded cells were examined. Surface-bound 45Ca2+ was removed by pretreatment with trypsin in EDTA buffer. During the first 6 min, basal efflux of 45Ca2+ occurred at a constant rate (0.24 min-1) at 37 degrees C. Addition of TRH (5 X 10(-7) M) resulted in an immediate enhancement of 45Ca2+ release representing about 20% of the remaining cellular 45Ca2+. In the same experiments PRL secretion increased by 45%. The EDTA in the external medium reduced the basal rate of 45Ca2+ release by 60%, but did not apparently affect the TRH-stimulated release. Somatostatin (10(-6) M) and verapamil (5 X 10(-5) M) inhibited both basal and TRH-stimulated PRL secretion, whereas high extracellular concentration of K+ (5 X 10(-2) M) had a stimulatory effect. However, neither of these treatments changed cellular 45Ca2+ release. Interference with energy-dependent Ca2+ transport by using metabolic inhibitors (iodoacetate, 6 X 10(-3) M; and antimycin, 2 X 10(-6) M) or by replacing Na+ in the medium by choline or by lowering the incubation temperature from 37 to 25 degrees C, had no effect on TRH-stimulated 45Ca2+ release although basal and TRH-stimulated PRL secretion were reduced. Thus, TRH apparently releases 45Ca2+ from calcium binding sites in the cell membrane.     

Hypothalamus-pituitary-thyroid axis interactions with pineal gland in the rat.

We examined in the rat several possible relationships between the pineal gland and the hypothalamus-pituitary-thyroid axis. The pineal gland, the retina, and the hypothalamus exhibited a diurnal rhythm in thyrotropin-releasing hormone (TRH) content with peak values occurring around 1200 h. This rhythm in the hypothalamus was abolished by constant light but was not affected by pinealectomy. Nor did pinealectomy affect hypothalamic TRH content, pituitary content of thyroid-stimulating hormone (TSH) or prolactin; serum levels of (TSH), triiodothyronine (T3), or thyroxine (T4), or serum free-thyroxine index; or free-triiodothyronine index. Melatonin did not affect TSH or prolactin release from the anterior pituitary or TRH release from the hypothalamus in vitro. Isoproterenol did not affect the TRH content of pineal glands in vitro; nor did TRH or T3 affect basal or stimulated activities of serotonin N-acetyltransferase, the presumed controlling enzyme in melatonin production. We found no evidence for significant interactions between the pineal gland and the hypothalamus-pituitary-thyroid axis.     

Effects of thyroliberin and 4-aminopyridine on action potentials and prolactin release and synthesis in rat pituitary cells in culture

Effects of thyroliberin (TRH) and 4-aminopyridine (4AP) were studied on prolactin (PRL) secreting rat pituitary tumour cells in culture (GH₃ cells). Intracellular recordings obtained from the same cell before and during TRH stimulation showed this peptide to increase the spontaneous firing frequency and prolong the Ca²⁺ dependent action potentials. These effects were mimicked by 4 AP, which acts by interfering selectively with voltage dependent ionic channels without affecting resting membrane properties. Optimal doses of TRH and 4AP approximately doubled the release of PRL. In contrast, TRH increased PRL synthesis 1.9-fold while 4AP had no effect. Increased PRL synthesis is thus not a direct consequence of the hormone release. We conclude that TRH and 4AP both stimulates PRL release via the facilitating effects on the action potentials. TRH has additional intracellular effects which lead to increased synthesis of the hormone. The effects of TRH responsible for stimulation of PRL synthesis are not causally related to the impulse activity of the surface membrane of the cell.     

Prolactin secretion in the empty sella syndrome, in prolactinomas and in acromegaly

Prolactin (PRL) secretion was studied in 47 patients with empty sella syndrome. Hyperprolactinemia (39-123 micrograms/l) was found in six of them. Intermittent increases in PRL were noted in another seven patients. In most subjects with empty sella syndrome and hyperprolactinemia, diurnal PRL variation was altered or impaired whereas the PRL response to TRH and L-dopa was normal. Low doses of bromocriptine (3.75-5 mg/day) normalized PRL. In patients with prolactinoma and acromegaly who had prolactin levels of 30-165 micrograms/l the diurnal PRL variation and PRL response to TRH were impaired. Patients with prolactinoma failed to suppress PRL during L-dopa test. The dose of bromocriptine required to normalize PRL ranged between 7.5 and 15 mg/day. It is concluded that in subjects with sellar changes and intrasellar cisternal herniation ("empty sella"), and with moderate increases in PRL, the responses to TRH and L-dopa and to bromocriptine may help to differentiate between the empty sella syndrome and a coexisting pituitary tumour.     

In vitro pituitary responsiveness to LHRH in young and old female rats. Influence of melatonin

The effect of aging and melatonin on in vitro pituitary responsiveness to luteinizing hormone-releasing hormone (LHRH) was studied. Young cyclic (3-months-old) control (cyclic-control, N = 15), and melatonin (MEL) treated for 2 months (150 microg/100 g BW) (cyclic-MEL, N = 15), old acyclic (23-months-old) control (acyclic-control, N = 13), and MEL-treated (acyclic-MEL, N = 18) rats were used. The hormones analyzed were luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL). The results showed a different influence of the reproductive status as well as of melatonin on the basal secretion rate of both gonadotropins, i.e. LH and FSH. Only the basal FSH release was significantly reduced in cyclic-MEL and acyclic-controls compared to cyclic-controls. The hemipitutary FSH content raised to values similar to those observed for FSH secretion and only the cyclic-MEL group showed significantly higher FSH pituitary content than for release. LHRH addition to the incubation medium resulted in increased LH release for both cyclic and acyclic rats, but FSH release was only stimulated in acyclic rats. Melatonin treatment blunted this response in both cases. In addition, melatonin treatment inhibited prolactin release in acyclic-MEL group after LHRH stimulation but not the basal levels. Pituitary LH and prolactin contents, were significantly higher than the pituitary LH and prolactin levels released from all groups studied, and were not affected by reproductive senescence nor by exogenous melatonin. These data indicate that aging influences more the secretory than the biosynthetic processes. Melatonin influences is endocrine status-dependent, being inhibitory when pituitary hormones reach their higher values.     

Modulation of G proteins and second messenger responsiveness by steroid hormones in GH3 rat pituitary tumour cells.

We have investigated the modulation of different G protein alpha- and beta-subunit levels in prolactin (PRL) and growth hormone producing rat pituitary adenoma cells (GH3 cells) in culture after prolonged exposure (6-48 h) to the steroid hormones 17 beta-oestradiol and dexamethasone. Gi-3 alpha- and G beta-subunits were the only G protein subunits which increased in response to 10(-6) M oestradiol (to approximately 150 and 200% of controls, respectively), while the other alpha-subunits investigated (Gs alpha, Gi-2 alpha and G(o) alpha) remained relatively unchanged. Thyroliberin (TRH)--and guanosine 5'-[beta gamma-imido]trisphosphate (Gpp(NH)p)-elicited adenylyl cyclase (AC) activities were reduced during 6-12 h of oestradiol treatment (by 60 and 20%, respectively), while the inhibitory effect of somatostatin (SRIF) increased by approximately 100%. Dexamethasone (10(-6) M) increased levels of the stimulatory G protein Gs alpha (to approximately 340%) and decreased levels of Gi-3 alpha (to 25%). After 48 h, the AC response to TRH was reduced by approximately 70%, whereas the effect of the other modulators remained close to controls. We conclude that G protein subunits in GH3 cells are subject to specific regulation by steroid hormones and that this may be important in the tuning of the responsiveness of PRL secretion to hormones in the in vivo situation.     

Pituitary-thyroid function and thyrotropin, prolactin and growth hormone responses to TRH in patients with chronic alcoholism

Basal plasma concentrations of thyroxine (T4), 3,3',5-triiodothyronine (T3), free T4 index (TF4I), free T3 index (FT3I) reverse T3, 3,3',5-triiodothyronine (rT3), resin T3 uptake (TR3U), thyroxine-binding globulin (TBG), thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) as well as thyrotropin releasing hormone (TRH) stimulated TSH, PRL and GH were investigated in 31 consecutive male patients (mean age 41 years) with chronic alcoholism. According to the histology of their liver biopsies the patients were divided into three groups: patients with normal livers, steatosis and cirrhosis. The control group consisted of 30 healthy males. The patients had abstained from alcohol for at least one week when studied, and they were on a nutritionally adequate diet. All had consumed a daily minimum of 52 g ethanol for at least 5 years. None of the patients had severe or decompensated liver disease. The patients had significantly reduced T3 and rT3 plasma levels compared to normals. Patients with cirrhosis of the liver had increased TBG and normal RT3U levels, while those without cirrhosis had increased RT3U and normal TBG levels. Plasma concentrations of basal as well as TRH-stimulated TSH and PRL were unchanged in alcoholic patients, whereas basal as well as stimulated GH levels were increased in cirrhotic alcoholics. It is concluded that alcohol per se influences T3 levels, but not the part of the hypothalamic-pituitary axis studied, and that the binding proteins are mostly determined by the degree of liver disease.     

Acute inhibition of PRL and TSH secretion after intraventricular injection of PRL in ovariectomized rats

Prolactin (PRL) is under short-loop inhibitory control via the hypothalamus. However, earlier studies evaluated the effects on PRL secretion of PRL levels elevated for periods of days. In this study we evaluated the acute effects of intraventricular and systemic injection of PRL on the release of a variety of pituitary hormones. Ovariectomized (OVX) rats, bearing implanted third ventricular and jugular cannulas were used. Blood was withdrawn in unanesthetized, freely moving animals before and after intraventricular injection of 0.9% NaCl or 1 or 3 micrograms of bovine (b) or ovine (o) PRL. Prolactin was also administered intravenously in doses of 3 or 6 micrograms. No effect on plasma levels of any of the pituitary hormones occurred after intraventricular or systemic injection of saline. Intraventricular injection of both doses of bPRL or oPRL significantly lowered plasma PRL within 15-30 min. In animals with elevated initial PRL values because of stress or estradiol (E) priming, greater lowering of PRL occurred. Inconsistent reductions in plasma PRL occurred after intravenous injection of oPRL but not bPRL, which elevated PRL values via cross-reaction in the immunoassay. In contrast, only small and inconsistent declines in luteinizing hormone (LH) were seen after intraventricular injection of PRL in either OVX or OVX E-primed rats. Plasma follicle-stimulating hormone (FSH) and growth hormone (GH) were not affected by PRL in any of the experiments; however, a significant lowering of thyrotropin (TSH) occurred in OVX or OVX E-primed rats within 30 min after intravenous injection of 3 micrograms of oPRL, but no change occurred after intravenous PRL. The data indicate that PRL can acutely inhibit PRL and TSH release via a hypothalamic action, whereas release of LH is only slightly inhibited and that of FSH and GH is unaltered.     

Combined pituitary function-test with four hypothalamic releasing hormones

Summary Anterior pituitary function was investigated in ten healthy subjects by administering a combination of 200 µg thyrotropin releasing hormone (TRH), 100 µg gonadotropin releasing hormone (GnRH), 100 µg growth hormone releasing factor (GRF^1–44), and 100 µg human corticotropin releasing factor (CRF). The same test protocol was performed in all subjects after pretreatment with 0.25 mg terguride. Five subjects were tested only with TRH and GnRH, five only with CRF, and six only with GRF. There was a prompt increase in all hormones after the administration of the four releasing hormones (RH). Pretreatment with terguride lowered the prolactin (PRL) increase (p<0.01) as well as the thyrotropin (TSH) peak (p<0.05) compared with the test without dopamine agonist pretreatment. The PRL levels after combined RH administration were significantly higher than after TRH and GnRH alone. Although four of the five subjects had higher TSH levels after combined RH administration than after TRH and GnRH alone, the difference was not significant. Other hormones were not significantly influenced by the combined RH administration or dopamine agonist pretreatment. Despite the fact that the interaction of the different releasing hormones and dopamine agonists influences the pituitary hormone response, combined RH administration seems to be a useful test for evaluating pituitary function also in patients receiving dopamine agonist therapy.Abbreviations ACTH Adrenocorticotropic hormone - CRF Human corticotropin releasing factor - DA Dopamine - FSH Follicle-stimulating hormone - GH Human growth hormone - GnRH Gonadotropin releasing hormone - GRF; GRF^1–44 Growth hormone releasing factor - LH Luteinizing hormone - PRL Prolactin - RH Releasing hormone (s) - RIA Radioimmunoassay - SE Standard error - TRH Thyrotropin releasing hormone - TSH Thyrotropin Supported by Deutsche Forschungsgemeinschaft (We 439/5-1 and Mu 585/2-2).