Zinc: an inhibitor of prolactin (PRL) secretion in humans

The response of plasma prolactin (PRL) to oral administration of increasing doses of zinc (25.0, 37.5 and 50.0 mg) was studied in 17 normal adult men and women. Blood samples were collected at 10 and 30-min intervals over a period of 120 min after two basal times (-30 and 0 min). PRL concentrations significantly fell below basal levels in all subjects in response to the increase in plasma zinc levels, as compared to the controls. These results suggest that acute hyperzincemia can inhibit basal PRL secretion in normal individuals.     

Gonadotropin, prolactin and thyrotropin pituitary secretion after exogenous dehydroepiandrosterone-sulfate administration in normal women.

The effect of exogenous dehydroepiandrosterone-sulfate (DHAS) on luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and thyroid-stimulating hormone (TSH) pituitary secretion was studied in 8 normal women during the early follicular phase. The plasma levels of these hormones were evaluated after gonadotropin-releasing hormone (GnRH)/thyrotropin-releasing hormone (TRH) stimulation performed after placebo or after 30 mg DHAS i.v. administration. The half-life of DHAS was also calculated on two subjects; two main components of decay were detected with half-times of 0.73-1.08 and 23.1-28.8 h. The results show an adequate response of all hormones to GnRH or TRH tests which was not significantly modified, in the case of LH, FSH and PRL, when performed in the presence of high levels of DHAS. However, the TSH response to TRH was significantly less suppressed (p less than 0.05) (39%) after DHAS administration than during repeated TRH stimulation without DHAS (51%). The data support the hypothesis that DHAS does not affect LH, FSH and PRL secretion, while TSH seemed to be partially influenced.     

人早孕子宫蜕膜催乳素分泌的调节

子宫内膜蜕膜化对胚泡植入与妊娠维持是非常重要的。为探讨蜕膜化维持的调节机制 ,本文研究了妊娠早期人子宫蜕膜细胞催乳素 (PRL)分泌的调节。结果表明 :(1)孕酮显著地刺激PRL的分泌。 (2 )雌激素的作用与其浓度有关 ,生理浓度的雌激素对PRL分泌无明显影响 ,而高水平的雌激素抑制孕酮的刺激作用。合适的雌孕激素比例对蜕膜化的维持是必要的。 (3)RU486明显地抑制PRL的分泌 ,故认为孕酮的作用至少是部分通过受体介导的机制。 (4 )高浓度的cAMP (≥ 10 -5mol/L)显著增加PRL的分泌 ,cAMP信号系统可能在蜕膜化反应中发挥重要作用。     

The influence of prolactin (PRL) on progesterone secretion by porcine luteal cells in vitro

Porcine luteal cells were obtained from corpora lutea on the 5th, 13th and 17th days of the estrous cycle. The cells were suspended at a concentration of 5 × 10⁴ cells/ml in Eagle's medium with 2% human serum albumin. These cells were incubated with or without 0.01, 0.1, 1 or 10 μg/ml porcine prolactin. The amount of progesterone in cultures was estimated by a radio-immunological method after 30 min, 3 h and 6 h of culturing.Luteal cells obtained on the 5th day of the estrous cycle and incubated without prolactin secreted 71.24 ± 21.91 ng progesterone/ml of medium, whereas under the influence of prolactin at 0.01, 0.1, 1 and 10 μg/ml, 39.06 ± 13.33, 44.31 ± 12.69, 44.88 ± 16.85 and 51.62 ± 15.01 ng progesterone/ml (P<0.01) were secreted. Luteal cells from the 13th day of the estrous cycle incubated without prolactin secreted on average 70.72 ± 9.21 ng progesterone/ml of medium, whereas under the influence of different prolactin doses 50.75 ± 8.52, 46.54 ± 7.13, 43.30 ± 6.78 and 41.68 ± 7.21 ng progesterone/ml (P<0.01) were secreted.Prolactin did not change progesterone secretion by luteal cells obtained on the 17th day of the estrous cycle. An influence of the incubation time on progesterone secretion by these cells was observed: after 30 min of incubation the cells secreted 8.83 ± 2.95 ng/ml, after 3 h 8.12 ± 2.57 ng/ml and after 6 h 6.86 ± 1.91 ng/ml, irrespective of the amount of PRL added.The results suggest that prolactin plays a role in the luteolysis of the corpus luteum.     

The role of estrogen in the TSH and prolactin responses to thyrotropin-releasing hormone in postmenopausal as compared to premenopausal women.

The basal and TRH (Thyrotropin-Releasing Hormone) stimulated TSH (Thyrotropin) and PRL (Prolactin) responses (incremental area; IA) to 200 micrograms TRH was studied in 13 pre- and 13 postmenopausal women of 60 years of age. Both groups consisted of healthy women, none had goiter and all were negative for thyroid autoantibodies. The serum levels of TSH, T3, T4 and SHBG (sex hormone-binding globuline) were in the normal range and did not differ significantly between the groups. There were no differences in basal TSH (1.3 +/- 0.5 vs 1.4 +/- 0.5 mIU/l) or PRL (6.4 +/- 2.7 vs 6.6 +/- 2.5 micrograms/l) or for PRL IA (498 +/- 126 vs 584 +/- 165) between pre- and postmenopausal women. However, for TSH IA there was a slight decrease (15%), but not significant, in the postmenopausal group compared to the premenopausal group (1630 +/- 598 vs 2067 +/- 893). In conclusion, a weak but not significant decrease in the TSH response to TRH in postmenopausal women may be explained by the lower endogenous estradiol level.     

Nocturnal hypoxia and prolactin secretion in obese women.

Respiration during sleep was studied in six obese women who had impaired prolactin response to insulin induced hypoglycaemia (non-responders), six obese women with a normal prolactin response to hypoglycaemia (responders), and six lean women. Sleep apnoea did not occur in any subject. All the obese women showed a decrease in haemoglobin oxygen saturation when asleep, which occurred predominantly during periods of rapid eye movement sleep. That the fall in oxygen saturation was significantly greater (p less than 0.05) in the obese non-responders suggests that central as well as mechanical factors may be important for the genesis of nocturnal hypoxia and is evidence for a disturbance of central nervous function in some obese women.     

Localization of thyrotropin (TSH) in the dog pituitary gland

Summary Using the immunoperoxidase technique and antisera to the specific beta () subunits of bovine and rat TSH¹, selective immunocytochemical staining was localized in a specific cell population in the pars distalis of the dog pituitary gland. These TSH cells were found to be positive to aldehyde fuchsin, alcian blue, periodic acid-Schiff (PAS) and aniline blue. With the performic acidalcian blue (pH 0.2) -PAS-orange G procedure these cells stained blue-purple, demonstrating FSH/LH cells (blue or turquoise), ACTH/MSH cells (redpurple) and PRL cells (orange-red). The TSH cells were further differentiated from other functional cell types of the pars distalis on the basis of their typical cytological features, intraglandular distribution and by immunocytochemical double staining. In the pars distalis of adult male dogs the TSH cells were mostly shown to be smaller in size and less numerous than in bitches in the anestrous phase of the sexual cycle. Moreover, cytological alterations in the immunoreactive thyrotrophs in the pituitary of male and female dogs generally paralleled the spontaneous changes in thyroid function associated with thyroid atrophy and/or pituitary insufficiency, and thyroid hyperplasia or goiter. In conclusion, because of their specificity and high potency, the antisera to the -subunits of bovine and rat TSH represent an effective tool for the selective immunocytochemical localization of TSH in the dog pituitary. This allows the study of the morphology and function of TSH cells under different physiological, pathological and experimental conditions.Abbreviations for Hormones cited in this Paper ACTH Adrenocorticotropin - FSH Follicle Stimulating Hormone - GH Growth Hormone - LH Luteinizing Hormone - MSH Melanocyte Stimulating Hormone - PRL Prolactin - TSH Thyrotropin - TRH TSH Releasing Hormone - CG Chorionic Gonadotropin The authors are grateful to Mrs. B. Schilk and Miss U. Tüshaus for their excellent technical assistance     

Endogenous expression of Neuregulin-1 (Nrg1) as a potential modulator of prolactin (PRL) secretion in GH3 cells

The binding of Neuregulin-1 (Nrg1) to the epidermal growth factor family of receptor tyrosine kinases (ErbB) mediates intercellular and intracellular communication and regulates a broad spectrum of biological processes, such as tumorigenesis and myelination. Recombinant Nrg1 has been shown to control prolactin (PRL) secretion from rat prolactinoma GH3 cells. However, the endogenous expression of Nrg1 and its role in PRL secretion in GH3 cells are not known. In this study, we demonstrate that type III Nrg1 isoforms are endogenously expressed in GH3 cells. An in vitro functional analysis by using short interfering RNA against Nrg1 has revealed that endogenous Nrg1 regulates PRL secretion from GH3 cells in part in an ErbB-3-receptor-dependent manner, with no significant effects on growth hormone secretion. Therefore, Nrg1 is a specific modulator of PRL secretion in GH3 cells. Additionally, the co-localization of Nrg1 and ErbB-2 receptor, which is shared by both ErbB-3 and ErbB-4 receptors in the formation of heterodimers, has been detected in one out of five human prolactinoma tissues. Our findings suggest that GH3 cells intrinsically express a group of type III Nrg1 isoforms that regulate PRL secretion through an autocrine/paracrine mechanism. Further investigation into the role of Nrg1 on PRL secretion should provide clues to advance the clinical management of prolactinoma.     

Growth hormone and prolactin secretion after metoclopramide administration (DA2 receptor blockade) in fertile women.

In this report, we will describe the results of a cross-sectional study to assess PRL and GH secretion during the early follicular phase in 22 fertile patients after metoclopramide administration in order to achieve a dopaminergic DA2 receptor blockade. Blood samples were collected at - 15, 0, 15, 30, 45 and 60 minutes. PRL, GH, estradiol, IGF-I, TSH, glucose, and insulin were measured in the samples taken at - 15 and 0 minutes. The existence of a correlation between GH and PRL secretion was investigated. All patients presented normal serum levels of estradiol, prolactin, insulin, fasting glucose and IGF-I. Serum GH levels were not changed after metoclopramide infusion (p = 0.302), but there was a significant alteration in serum PRL (p = 0.0001) with the highest levels after 30 (mean: 237.20 ng/ml +/- 95.86) and 45 (mean: 211.80 ng/ml +/- 83.24) minutes. Serum GH levels did not correlate with serum PRL levels after the dopaminergic DA2 blockade. We conclude that GH secretion was not modulated by a direct effect of type 2 dopamine receptor.     

Ultrastructural localization of thyrotropin (TSH) in the porcine anterior pituitary

Summary Two different immunocytochemical techniques based on specific antibodies against -subunits of porcine, rat and bovine TSH were applied at the ultrastructural level to identify the TSH cells in the porcine anterior pituitary and to compare the subcellular localization of the hormone.The post-embedding method on serial ultrathin sections revealed the localization of TSH in the granules of a specific cell type, negative for the other hormones. TSH was found in polyhedral cells characterized (i) by their content of granules that were the smallest of all the cell types examined, and (ii) by their flattened or slightly dilated RER cisternae. The pre-embedding method applied to isolated cells permitted a good penetration of antisera and the maintenance of antigenicity in sites inaccessible to the post-embedding method. Thus, immunoreactivity of TSH was detected in the secretory granules, the cytoplasmic matrix and in portions of the rough endoplasmic reticulum, in association with some membranes and inside some saccular structures.     

A novel polymorphism of the porcine prolactin gene (PRL)

Prolactin is a protein hormone playing a role in the maintenance of pregnancy in the pig by action on corpora lutea cells and possibly initiating production of progesterone. The prolactin gene is 10 kb in size and is composed of 5 exons and 4 introns. The present work is a report of the swine PRL gene--comparative DNA sequence analysis and the SNP revealed in the promoter region. Based on the bovine prolactin gene, three primer pairs were designed using the Primer3 on-line software. The overlapping fragments covered about 400 nucleotides of the promoter and 78 nucleotides of exon 1. The fragments were amplified; two of them were sequenced and deposited in the GenBank database (AY341908 and AY905690). All fragments were analyzed using multitemperature SSCP (MSSCP) technique. Only one fragment appeared to show a different MSSCP pattern. The samples of differing MSSCP conformers were sequenced and the C499T transition was identified in the 5'UTR region of the gene. The HphI restriction enzyme appeared to recognize the novel SNP. The alignment for homology analysis was performed with porcine, bovine (X01452) and human (NM_000948) DNA sequences available in GenBank database, using BLAST software. The comparative homology analysis results varied in dependence on the species and functional region of the gene.     

Possible binding site of thyrotropin binding inhibitor immunoglobulin (TBII) on the thyrotropin (TSH) receptor, which is different from TSH binding site

A synthetic decapeptide, P-194, which has the sequence No. 103 to 111 of hTSH receptor structure with an additional N-terminal tyrosine, did not bind TSH nor affected its receptor binding and thyroid stimulating activity. Preincubation of P-194 with sera from thyroid patients caused a significant decrease in TBII activity in almost all 12 TBII positive sera and an increase of thyroid stimulating activity in 3 of 7 Graves' IgG studied. In addition, [125I] P-194 bound to serum IgG fraction from thyroid patients with a positive correlation with TBII (N = 35, r = 0.509, p less than 0.01). The P-194 portion may be, at least a part of, TBII binding site distinct from the TSH binding site on the TSH receptor.     

The effect of L-DOPA administration on thyrotropin (TSH) and thyrotropin releasing hormone (TRH) levels in serum in primary or pituitary hypothyroidism.

The effect of acute administration of L-DOPA on TSH and TRH levels in serum was studied in primary or pituitary hypothyroidism. TRH levels in serum fell and then returned to initial levels after L-DOPA administration in primary or pituitary hypothyroidism. TSH levels in serum fell and then returned to initial levels after L-DOPA administration in primary hypothyroidism. T4 and T3 levels in serum did not change after L-DOPA administration in primary or pituitary hypothyroidism. These data suggested that L-DOPA might act directly to hypothalamus.