In vitro effects of CINC/gro, a member of the interleukin-8 family, on interleukin-6 secretion by rat posterior pituitary cells

We investigated the effects of CINC/gro on IL-6 secretion by rat posterior pituitary cells. CINC/gro immunoreactivity was already detected in 1-h conditioned medium of normal posterior pituitary cells, and it increased significantly in a time-dependent manner during the first 24 h of culture. This immunoreactivity could be induced by TNF-alpha in a dose-dependent manner. On the other hand, CINC/gro stimulated IL-6 secretion by posterior pituitary monolayer cultures in a concentration dependent manner. Thus, CINC/gro significantly (P < 0.01) increased the secretion of IL-6 within 13 h of incubation, and this effect continued throughout 24 h of incubation. The stimulatory effect of 100 ng/ml CINC/gro on IL-6 secretion was completely blocked by 24-h incubation with 100 ng/ml IAP. These data demonstrate a new biological activity for CINC/gro in the posterior pituitary system.     

Effect of endothelin-1 in man--impact on basal and stimulated concentrations of luteinizing hormone, follicle-stimulating hormone, thyrotropin, growth hormone, corticotropin, and prolactin

The effect of endothelin-1 on basal and stimulated serum (plasma) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH), prolactin (PRL), growth hormone (GH), and corticotropin was investigated in healthy male volunteers (n = 5). Intravenous (IV) administration of endothelin-1 (5 ng/kg/min for 15 minutes, followed by 2.5 ng/kg/min for 105 minutes) induced an increase in basal plasma concentrations of corticotropin. Serum concentrations of PRL, TSH, LH, FSH, and GH remained unchanged. The increase in serum concentrations of these pituitary hormones induced by IV administration of LH-releasing hormone ([LH-RH] 100 micrograms), thyrotropin RH ([TRH] 400 micrograms), GH-RH (100 micrograms), and corticotropin-releasing factor ([CRF] 100 micrograms) was suppressed in regard to PRL (P < .01) and GH (P < .01) and enhanced in regard to corticotropin (P < .01). Stimulated serum concentrations of LH and FSH also tended to be higher following administration of endothelin-1 (P < .05), whereas the increase in serum concentrations of TSH remained unchanged. Thus, when administered in pharmacological doses, endothelin-1 influences pituitary hormone secretion in man.     

Effects of growth hormone, prolactin, insulin-like growth factors, and gonadotropins on progesterone secretion by porcine luteal cells

Growth hormone (GH) and IGF-I have receptors within the corpus luteum (CL) and stimulate CL function. Our objective was to investigate the effects of GH, prolactin (PRL), IGF-I, IGF-II, LH, and FSH on progesterone secretion by porcine luteal cells during mid-pregnancy. Gilts (crossbred Yorkshire/Landrace) were slaughtered on d 44 of pregnancy and CL were collected. Large and small luteal cells (LLC and SLC, respectively) were obtained from dissociated CL and separated by elutriation. Luteal cells were incubated with 0, 1, 10, or 100 ng/mL of GH, PRL, IGF-I, IGF-II, LH, and FSH or combinations of 10 ng/mL of these reagents for 24 or 48 h. Culture media were harvested and concentrations of progesterone analyzed by radioimmunoassay. Growth hormone, PRL, and IGF-I increased (P < .05; 100 ng/mL dose) concentrations of progesterone in media of LLC. Insulin-like growth factor-II, LH, and FSH had no effect on progesterone in LLC cultures. In SLC cultures, GH, PRL, IGF-I, IGF-II, and FSH failed to stimulate progesterone secretion, whereas LH increased progesterone secretion (linear effect of dose; P < .05). Combinations (10 ng/mL each hormone) of GH and IGF-I or PRL and IGF-I increased progesterone secretion by LLC compared with control, GH, PRL, or IGF-I alone (P < .05). Similar combinations of GH or PRL with IGF-I had no effect on SLC. Conclusions are that GH and PRL are stimulatory to progesterone secretion by LLC (location of GH receptor) and SLC are responsive to LH during mid-pregnancy. Both GH and PRL are synergistic with IGF-I for increased progesterone secretion.     

Effects of cannabinoids on prolactin and gonadotrophin secretion: involvement of changes in hypothalamic gamma-aminobutyric acid (GABA) inputs

CB1 cannabinoid receptors are located in hypothalamic nuclei and their activation alters several hypothalamic neurotransmitters resulting in, among other things, decreased prolactin (PRL) and luteinizing hormone (LH) secretion from the anterior pituitary gland. In the present study, we addressed two related objectives to further explore this complex regulation. First, we examined whether changes in gamma-aminobutyric acid (GABA) and/or dopamine (DA) inputs in the medial basal hypothalamus might occur in parallel to the effects resulting from the activation of CB1 receptors on PRL and gonadotrophin secretion in male rats. Thus, the acute administration of (-)-delta9-tetrahydrocannnabinol (delta9-THC) produced, as expected, a marked decrease in plasma PRL and LH levels, with no changes in follicle-stimulating hormone (FSH) levels. This was paralleled by an increase in the contents of GABA, but not of DA, in the medial basal hypothalamus and, to a lesser extent, in the anterior pituitary gland. The co-administration of delta9-THC and SR141716, a specific antagonist for CB1 receptors, attenuated both PRL and LH decrease and GABA increase, thus asserting the involvement of the activation of CB1 receptors in these effects. As a second objective, we tested whether the prolonged activation of these receptors might induce tolerance with regard to the decrease in PRL and LH release, and whether this potential tolerance might be related to changes in CB1-receptor binding and/or mRNA expression. The chronic administration of R-methanandamide (AM356), a more stable analog of anandamide, the putative endogenous cannabinoid ligand, produced a marked decrease in plasma PRL and LH levels, with no changes in FSH. The decreases were of similar magnitude to those caused by a single injection of this cannabimimetic ligand, thus suggesting the absence of tolerance. In parallel, the analysis of CB1-receptor binding and mRNA expression in several hypothalamic structures proved that the acute or chronic administration of AM356 did not affect either the binding or the synthesis of these receptors. In summary, the activation of CB1 receptors in hypothalamic nuclei produced the expected decrease in PRL and LH secretion, an effect which might be related to an increase in GABAergic activity in the hypothalamus-anterior pituitary axis. The prolonged activation of these receptors for five days did not elicit tolerance in terms of an attenuation in the magnitude of the decrease in PRL and LH, and, accordingly, did not alter CB1-receptor binding and mRNA levels in the hypothalamic nuclei examined.     

Ipamorelin, the first selective growth hormone secretagogue

The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1. In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%). A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anaesthetised rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml). In conscious swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma. Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine. None of the GH secretagogues tested affected FSH, LH, PRL or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol. Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation. This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release. In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of ipamorelin makes this compound a very interesting candidate for future clinical development.     

Endocrinological evaluation of sellar and suprasellar tumor cases (the sixth report)-on pituitary hormone secretion of acromegalic patients before treatment (author's transl)

1) Pituitary hormone secretion of 14 acromegalic patients was studied before treatment. Incidence of hyporeactive response was 0%, 43%, 29%, 71% and 9% in ACTH, LH, FSH, TSH and PRL respectively. 2) Relatively higher incidence of hyporeactive TSH response in TRH test seems to be characteristic in acromegalic patients. 3) Six of 13 acromegalic patients examined on blood PRL level revealed relatively high blood PRL level over 50ng/ml.     

The 24-hour rhythms in plasma growth hormone, prolactin and thyroid stimulating hormone: effect of sleep deprivation

Twenty-four hour secretory rhythms of growth hormone (GH), prolactin (PRL) and thyroid stimulating hormone (TSH) were investigated in 9 normal adult men by means of serial blood sampling at 30 min intervals. The profiles of pituitary hormones were compared in 6 subjects between in normal nocturnal sleep condition and in delayed sleep condition. Plasma GH was measured with use of highly sensitive enzyme immunoassay (EIA) recently developed. Plasma TSH was also evaluated by highly sensitive time-resolved fluorometric immunoassay (TR-FIA). Time series analysis of plasma GH and PRL was performed by auto- and cross- correlation and spectral analysis. The detection limit of EIA for GH was 0.3 pg/ml and all plasma GH levels were within the detectable range of this EIA. Cross-correlation and spectral analysis suggested the presence of approximately 2-3 h rhythmicity of plasma GH. Plasma PRL appeared to have some 24-hour rhythmicity besides its sleep-dependent component. Sleep deprivation caused marked elevation of plasma TSH during night time. It is suggested that there appears two mechanisms regulating GH secretion: one has a sleep-independent and ultradian rhythm and another has a sleep-dependent rhythm.     

131I therapy for pediatric thyroid cancer

Azido-3'-deoxy-thymidine (AZT) is a drug extensively used in the treatment of AIDS. AZT was incubated in vitro either with the pituitary-hypothalamus complex (PHc) or the intact pituitary (PI) of male rats. The PHc is comprised of the hypothalamus and the attached pituitary gland. After a preincubation period, the PHc or PI was incubated for 1 or 2 h with Krebs-Ringer bicarbonate buffer or either of two different concentrations of AZT (1 and 10 microM). In the control incubations, the PHc released less prolactin (PRL) and more follicle-stimulating hormone (FSH) and luteinizing hormone (LH) than the PI, indicating that hypothalamic control of the pituitary was exerted in vitro, presumably by diffusion of releasing and inhibiting hormones from the neurohypophysis to the anterior lobe of the hypophysis. Both concentrations of AZT evoked a significant increase in release of PRL and a decreased release of LH and FSH from the PHc. In the case of LH, the higher concentration of AZT partially suppressed LH release within 1 h. The other effects were not dose-related and were observed after incubating the tissue with AZT for 2 h. However, incubation of the PI with AZT failed to alter anterior pituitary hormone release, illustrating that the site of action of AZT is in the hypothalamus. We hypothesize that AZT blocks DNA synthesis resulting in suppression of synthesis and consequent release of hypothalamic hormones that control release of pituitary hormones in vitro. The results raise the possibility that AZT may alter hypothalamic-pituitary function in vivo.     

Circadian responsiveness of the hypothalamic-pituitary axis

Five healthy men 25-38 years old were subjected to simultaneous composite intravenous stimulation tests of insulin hypoglycemia (0.1 U/kg), thyrotropin-releasing hormone (TRH, 100 mug), and luteinizing hormone-releasing hormone (LHRH, 50 mug) at weekly intervals to study the circadian responsiveness of the hypothalamic-adenohypophyseal axis at 0600, 1200, 1800, and 0000 hours. Blood sugar (BS), LH, follicle-stimulating hormone, TSH, prolactin, cortisol (C), growth hormone, and testosterone (T) levels were estimated before and after the administration of drugs. Comparisons were made between basal and delta values (difference between basal and peak or nadir levels) at different tests. Significant circadian variations in BS, GH, C, and, to a lesser extent PRL, responses were observed 0600 h basal and delta BS values were the lowest, delta BS was highest at 0000 h accompanied by maximal hypoglycemic symptoms; the delta values of both C and GH were significantly higher at 0600 h and 0000 h; highest mean delta PRL was observed at 0600; at 1800 h the basal plasma PRL level was maximum but the delta PRL was lowest. Plasma TSH, LH, and FSH responses did not show significant circadian variations. These results suggest that circadian variations are evident when stimuli act through central or hypothalamic mechanisms; however, direct stimulation of the adenohypophysis resulted in indentical responses at different periods tested.     

Assessment of pituitary function after transsphenoidal hypophysectomy in beagle dogs

Pituitary function was assessed in healthy adult beagle dogs before and after hypophysectomy. Anterior pituitary function was tested by use of the combined anterior pituitary (CAP) function test, which consisted of sequential 30-sec intravenous injections of four hypothalamic releasing hormones, in the following order and doses: 1 microgram of corticotropin-releasing hormone (CRH)/kg, 1 microgram of growth hormone-releasing hormone (GHRH)/kg, 10 micrograms of gonadotropin-releasing hormone (GnRH)/kg, and 10 micrograms of thyrotropin-releasing hormone (TRH)/kg. Plasma samples were assayed for adrenocorticotropin (ACTH), cortisol, GH, luteinizing hormone (LH), and prolactin (PRL) at multiple times for 120 min after injection. Pars intermedia function was assessed by the alpha-melanotropin (alpha-MSH) response to the intravenous injection of the dopamine antagonist haloperidol in a dosage of 0.2 mg/kg. Posterior pituitary function was assessed by the plasma vasopressin (AVP) response to the intravenous infusion of 20% saline. Basal plasma ACTH, cortisol, thyroxine, LH. PRL, and AVP concentrations were significantly lower at 10 wk after hypophysectomy than before hypophysectomy. In the CAP test and the haloperidol test, the peaks for the plasma concentrations of ACTH, cortisol, GH, LH, PRL, and alpha-MSH occurred within 45 min after injection. At 2 and 10 wk after hypophysectomy, there were no responses of plasma GH, LH, PRL, and alpha-MSH to stimulation. In four of eight hypophysectomized dogs, there were also no plasma ACTH and cortisol responses, whereas in the other four dogs, plasma ACTH and cortisol responses were significantly attenuated. The basal plasma ACTH and cortisol concentrations were significantly lower in the corticotropic nonresponders than in the responders. Plasma AVP responses were completely abolished by hypophysectomy, although water intake by the dogs was normal. Histopathological examinations at 10 wk after hypophysectomy revealed that adrenocortical atrophy was much more pronounced in the corticotropic nonresponders than in the responders. No residual pituitary tissue was found along the ventral hypothalamic diencephalon. However, in all hypophysectomized dogs that were investigated, islets of pituitary cells were found embedded in fibrous tissue in the sella turcica. A significant positive correlation was found between the number of ACTH-immunopositive cells and the ACTH increment in the CAP test at 10 wk after hypophysectomy. It is concluded that 1) stimulation of the anterior pituitary with multiple hypophysiotropic hormones, stimulation of the pars intermedia with a dopamine antagonist, and stimulation of the neurohypophysis with hypertonic saline do not cause side effects that would prohibit routine use, 2) in the routine stimulation of the anterior pituitary and the pars intermedia, blood sampling can be confined to the first 45 min, 3) the ACTH and cortisol responses to hypophysiotropic stimulation are the most sensitive indicators for residual pituitary function after hypophysectomy, 4) small islets of pituitary cells in the sella turcica, containing corticotropic cells, are the most likely source of the attenuated corticotropic response that may occur after hypophysectomy, and 5) residual AVP release from the hypothalamus after hypophysectomy is sufficient to prevent diabetes insipidus, despite the fact that the AVP response to hypertonic saline infusion is completely abolished.     

Follicle-stimulating hormone, human chorionic gonadotropin, and prolactin receptors in hamster corpora lutea or dispersed luteal cells during pregnancy

In vitro progesterone (P4) production by hamster luteal cells is stimulated throughout pregnancy by FSH and LH. Prolactin (PRL) by itself, however, increases P4 synthesis only on Day 12; on Day 4, FSH+LH+PRL induces optimal P4 secretion [Biol Reprod 1994; 51:43-49]. In light of these findings, in this study we investigated FSH, hCG, and PRL receptors in hamster CL or dispersed luteal cells on Days 4, 8, and 12 of pregnancy. Scatchard analysis of hamster CL on Days 4 and 8 showed considerably more unoccupied hCG receptors than FSH receptors: on Day 4, there was 9.5 fmol/mg protein for FSH binding sites vs. 1741 fmol/mg protein for hCG binding. Moreover, the binding affinity of hCG was greater than for FSH: the Day 4 Kd was 0.136 nM for hCG vs. 0.308 for FSH. Similar differences were observed on Day 8. Dispersed luteal cells (large+small cells) were incubated for 24 h with or without 10 ng of ovine FSH, LH, and PRL or human recombinant FSH (r-hFSH), alone or in different combinations. The cells were then washed and incubated for 4 h with iodinated hCG, FSH, or PRL with or without 100-fold excess of unlabeled hormones. The number of binding sites per 200,000 luteal cells did not change appreciably for FSH and hCG on Days 4 and 12 of pregnancy, whereas PRL binding sites significantly increased on Day 12.(ABSTRACT TRUNCATED AT 250 WORDS)     

Establishment of functional human pituitary tumor cell cultures

Five primary human pituitary tumor cell cultures were initiated from adenoma fragments obtained from patients with prolactin-secreting adenomas and acromegaly. Functional cell cultures were maintained and propagated in monolayer or suspension culture for up to 9 months. Optimal cell viability and growth were achieved using Ham's F10 medium enriched with 20% fetal bovine serum, although cells from a patient with acromegaly also grew in serum-free, defined, hormone-containing medium. Bromocriptine (100 ng/ml) did not alter the growth curve of replicating cells derived from a patient with acromegaly. These cells initially secreted 5.5 micrograms human growth hormone/10(6) cells, and hormone production diminished after 6 wk. Prolactin secretion by cells derived from prolactinomas (0.5 to 1.3 micrograms/10(6) cells/24 h) was stimulated by thyrotropin-releasing hormone (10 ng/ml) in two of the cultures. Both dopamine (10 ng/ml) and nickel chloride (1 mM) suppressed PRL secretion. These studies demonstrate that responsive human pituitary tumor cell cultures can be initiated and maintained.     

Identification of mammosomatotrophs in the turkey hen pituitary: increased abundance during hyperprolactinemia

We have previously reported that the hyperprolactinemia in incubating turkey hens is associated with recruitment of lactotrophs in the pituitary gland. In this study we have used double immunofluorescence and in situ hybridization histochemistry to 1) identify mammosomatotrophs in the anterior pituitary gland of egg-laying turkey hens and incubating hens, and 2) verify PRL gene expression within mammosomatotrophs by colocalizing PRL messenger RNA in GH-immunoreactive (ir) cells. The pituitaries of laying and incubating turkey hens were collected, and the midsagittal sections were dual labeled for either PRL and GH or PRL messenger RNA and GH. The plasma PRL concentrations were higher in incubating hens (231 +/- 10.6 ng/ml) than in laying hens (43 +/- 7.4 ng/ml; P < 0.01). In the midsagittal pituitary sections, mammosomatotrophs were predominantly found scattered in the caudal lobe of the anterior pituitary gland, in the ventral half of the cephalic lobe, and at the junction of cephalic and caudal lobes. In incubating hens, the proportion of mammosomatotrophs was 7.4 +/- 1.52% (mean +/- SEM) of the total number of GH-ir and/or PRL-ir cells counted, which was significantly higher (P < 0.05) than that found in laying hens (0.6 +/- 0.23%). Furthermore, PRL gene expression was observed in many GH-ir cells in the incubating hen pituitary gland. These data suggest that 1) mammosomatotrophs are present in the turkey pituitary gland, and 2) there is an increased abundance of mammosomatotrophs in the incubating turkey hen that may contribute to hyperprolactinemia.     

Recurrent goiter, hyperthyroidism, galactorrhea and amenorrhea due to a thyrotropin and prolactin-producing pituitary tumor

A 22-year-old woman with recurrent goiter, hyperthyroidism, galactorrhea, and amenorrhea due to a pituitary tumor is described. She had been treated surgically twice for recurrent goiter with tracheal compression. Despite clinical signs of hyperthyroidism and slightly elevated plasma thyroid hormone levels (T4: 11 mug/dl; T3: 189 ng/dl), without thyroid hormone replacement therapy the basal TSH level was elevated up to 23 muU/ml and could not be suppressed by exogenous thyroid hormones: even when the serum thyroid hormone levels were raised into the thyrotoxic range (T4: 16.2 mug/dl T3: 392 ng/dl), the basal TSH fluctuated between 12 and 29 muU/ml. The basal PRL level was elevated up to 6000 muU/ml. The administration of TRH (200 mug iv) led only to small increments of TSH and PRL levels. Bromocriptin (5 mg p.o.) or l-dopa (0.5 g p.o.) suppressed TSH and PRL values significantly. After transsphenoidal hypophysectomy, TSH and PRL were below normal and the patient development panhypopituitarism. The adenoma showed two cell types which could be identified as lactotrophs and thyrotrophs by electronmicroscopy and immunofluorescence. From these data we conclude that the patient had a pituitary tumor with an overproduction of thyrotropin and prolactin.     

Food restriction differentially affects mRNAs encoding the major anterior pituitary tropic hormones

Chronic food restriction (FR) leads to adaptive cellular changes, some of which retard aging. Moreover, some of these changes occur within weeks after onset of FR. Because neuroendocrine mechanisms may mediate these effects, we measured the effect of FR on the messenger ribonucleicacids (mRNAs) encoding all of the tropic hormones of the anterior pituitary (AP). Slot blot and solution hybridization were conducted on AP ribonucleicacid (RNA) samples obtained at 0500 h (AM) and 1500 h (PM) from 3-month-old male Fischer 344 rats fed ad libitum (AL) or FR (60% of AL calories) since 6 weeks of age. PolyA RNA/microgram total RNA was similar in AL and FR rats, indicating that there was no overall effect of FR on mRNA levels. The level of proopiomelanocortin (POMC) mRNA was not reduced by FR when expressed per microgram of RNA or as total AP content. By contrast, the total AP content of the mRNAs encoding LH beta, FSH beta, TSH beta, GH, and PRL was markedly reduced by FR. When expressed per microgram of RNA, however, only GH (AM and PM), FSH beta (AM), TSH beta (PM), and PRL (PM) were reduced by FR. These results reveal that FR differentially affects pituitary tropic hormone mRNA levels within weeks after onset of FR, and are consistent with a role for neuroendocrine alterations in the initiation of adaptive cellular responses to FR.     

Androgen receptors in the anterior pituitary and central nervous system of the androgen "insensitive" (Tfm) rat: correlation between receptor binding and effects of androgens on gonadotropin secretion

The cytosol fractions of the anterior pituitary, hypothalamus, preoptic area and brain cortex of androgen "insensitive" (Tfm) rats possess androgen receptors. However, in the Tfm rats the androgen binding per mg protein was only 10-15% of that in the corresponding normal littermates (Nl). The physicochemical properties of the androgen receptors in the anterior pituitary of the Tfm rat were indistinguishable from those of the normal rat. Thus, no distinctive differences were observed with regard to electrophoretic mobility in 3.25% polyacrylamide gels, isoelectric point (pI=5.8), binding affinity (KD=1.5 X 10(-9)M), temperature stability, sulfhydryl dependence and steroid specificity. It is, therefore, likely that the very low androgen binding capacity by the anterior pituitary and the central nervous system is due to an extreme reduction in the receptor number rather than to the presence of abnormal receptors. Since in the Tfm animals the androgen receptor number is reduced by 85-90%, it is to be expected that very high doses of androgens would be required to achieve hormonal effects. In fact, low doses of 5alpha-dihydrotestosterone propionate (50 mug/100 g body weight) given sc daily for 12 days had no effect on serum levels of LH and FSH. However, very high doses (2 mg/100 g body weight) of testosterone propionate and 5alpha-dihydrotestosterone propionate, which maintained circulating androgen levels above 20 ng/ml, significantly reduced serum gonadotropin levels in castrated Tfm rats. In normal littermates both low and high doses of the androgens suppressed gonadotropin secretion to low levels. These findings strongly indicate that androgen receptors are essential to androgen action on the anterior pituitary and central nervous system in the rat. The serum levels of testosterone (7.7+/-0.15 (SE) ng/ml) and 5alpha-dihydrotestosterone (0.37+/-0.06 ng/ml) were significantly higher in intact Tfm rats than in normal littermates (2.6+/-0.03 and less than 0.1 ng/ml, respectively). The failure of the elevated concentrations of serum androgens to reduce the high serum levels of LH and FSH in intact Tfm rats is most likely due to the extreme reduction of the androgen receptor number and the consequent insufficient hypothalamic and/or pituitary response to androgens.     

The use of a curved ophthalmic blade to facilitate incising Mohs micrographic sections with the desired bevel despite anatomic obstructions

To establish whether nitric-oxide (NO) participates in the regulation of prolactin (PRL) secretion in humans in basal conditions and/or under stimulation with vasoactive intestinal polypeptide (VIP), seven normal men were treated with a placebo (normal saline) or the NO synthase (NOS) inhibitor L-NAME (40 microg/kg injected plus 50 microg/kg infused intravenously over 60 minutes), which in previous studies has been found able to modify other pituitary hormone secretions. Experiments were performed either in basal conditions or during stimulation of PRL secretion with an intravenous infusion of VIP (4 pmol/kg min over 60 minutes). The administration of L-NAME was unable to change the basal secretion of PRL. In contrast, L-NAME significantly enhanced the PRL increase induced by VIP. These data argue against an involvement of NO in regulation of basal PRL secretion. In contrast, the stimulatory effect of L-NAME on VIP-induced PRL secretion suggests that NO exerts an inhibitory control of the PRL response to VIP.     

The effect of thyrotropin-releasing hormone on gonadotropin and free alpha-subunit secretion in patients with acromegaly and functionless pituitary tumors

Paradoxical response of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and alpha-subunits (alpha-SU) to thyrotropin-releasing hormone (TRH) have previously been reported in individuals with clinically nonfunctioning pituitary tumors (NFT). In the present study, we assessed the in vivo responses of LH, FSH, alpha-SU to TRH in 34 patients with NFT and 29 patients with agromegaly. Twenty-three clinically NFT were postoperatively analyzed by immunocytochemistry and 21 stained positive for beta-FSH and/or beta-LH. Two patients with NFT had elevated basal circulating levels of FSH (41.5 IU/L) and thus were characterized as FSH-secreting adenomas. TRH in these patients increased LH from basal 1.6 IU/L to 32.6 IU/L. In other patients with NFT, circulating levels of glycoprotein peptides were not elevated. TRH induced significant rise of LH in 8 (23.5%), FSH in 5 (14.7%), and alpha-SU in 10 (29.4%) patients with NFT. Thus, a bolus dose of TRH elicited a notable increment in FSH, LH or alpha-SU in 23 of 34 patients with NFT. Among 29 patients with acromegaly, LH rose in 6 (20.7%), FSH in 5 (17.2%), and alpha-SU in 3 (10.3%) patients. In conclusion: (1) We confirm that most NFTs are capable of synthesizing gonadotropin hormones and subunits (beta-FSH, beta-LH). (2) Most patients in our study responded by either FSH, LH or alpha-SU secretion after TRH, independent of basal hormone levels. Furthermore, recent studies show that by measurement of TRH stimulated beta-FSH and beta-LH one might further improve the diagnostic tools. (3) Gonadotropin response and possibly alpha-SU to TRH are also found in some patients with acromegaly. This could be a marker of a plurihormonal pituitary tumor.