Pituitary hormones dependent expression of insulin-like growth factors I and II in the immature hypophysectomized rat testis.

Since insulin-like growth factors I (IGF-I) and II (IGF-II) appeared involved in paracrine or autocrine regulation of both cell multiplication and differentiation of the rat testis, we have investigated the pituitary hormonal dependence of IGF-I and IGF-II mRNA production in the testis of immature hypophysectomized rats (22 days old) supplemented with highly purified FSH, LH, GH or PRL. Our data show that testicular expression of IGF-I mRNA as measured by dot-blot hybridization, is increased by LH, FSH or GH treatments of 7-, 6-, and 4-fold, respectively, above controls. Intensity of the signal was 3-fold lower after PRL treatment than in hypophysectomized control rats. On the contrary, IGF-II mRNA expression, was found low in the immature hypophysectomized rat testis and unmodified by any hormonal treatment. In contrast to the increase of IGF-I expression in the testis no significant change in the IGF-I plasma concentration was observed after LH or FSH supplementation. GH treatment, as expected, increased 4-fold the IGF-I plasma concentration of the experimental animals. Since we have previously shown that LH, FSH, and GH exhibit selective cell multiplication and differentiation in the testis of our animal model, it is proposed that testicular IGF-I expression could be the tissue response to pituitary hormone in these phenomena.

Expression and functionality of luteinizing hormone/chorionic gonadotropin receptor in the rat prostate.

In addition to androgens that are essential for maintenance of prostate growth and function, nonandrogenic hormones must also be considered to explain some regulatory events occurring in the prostate. The detection of LH/CG receptor (LH/CG-R) gene expression in some nongonadal tissues, has led us to consider LH as a potential regulatory factor of prostatic development and function. In this study, we have demonstrated by RT-nested polymerase chain reaction and Northern blotting that the rat prostate contains the same LH/CG-R transcript as the gonads. Western immunoblotting, ligand blotting, and binding analysis have shown that rat prostate also contains a 93-kDa receptor protein that is able to bind [125I]hCG specifically and with a high affinity (6.0 x 10(9) M-1). Our results also indicated that the concentration of binding sites was lower in the prostate than in the gonads. LH/CG-R sites of expression have been localized in the prostate by immunohistochemistry: specific staining was observed in all the epithelial cells of the gland, but the ventral lobes are much more immunoreactive than the lateral and dorsal lobes. Finally, the ability of this prostatic LH/CG-R to induce a physiological response was evaluated in an explant culture system. A time course experiment was carried out, and we observed a significant dose-dependent stimulation of cAMP production after 3 h of treatment: 3.0 +/- 0.4, 4.2 +/- 0.4, and 5.0 +/- 0.5 pmol/ml of cAMP for 0, 100, and 500 ng/ml of LH, respectively. In conclusion, LH is able to act directly on the prostatic gland through specific receptors that are structurally and functionally very similar to those expressed in the gonads and are mainly localized in the ventral lobe of the organ. These data suggest that LH plays a significant physiological role in the prostate.

Dose-dependent effects of human prolactin on the immature hypophysectomized rat testis.

We have studied dose-dependent effects of highly purified human PRL (39 IU/mg) on the testis of immature (22-day-old) hypophysectomized rats daily supplemented for 7 days with 2, 10, or 30 micrograms hormone. Dose-dependent stimulation was observed for all parameters: testis weight (1.6- and 2-fold above control for 10 and 30 micrograms PRL), basal and hCG-stimulated testosterone (14- and 21-fold), intratesticular testosterone (7- and 21-fold) and estradiol (1.2- and 1.5-fold), LH receptor concentration (1.8- and 2.5-fold), in vitro pregnenolone production by cholesterol side-chain cleavage enzyme (3-, 5- and 7-fold), and aromatase activity (2.1- and 2.4-fold). The number of Leydig cells exhibiting immunoreactivity toward anti-P450scc, anti-P450(17 alpha), and anti-3 beta-hydroxysteroid dehydrogenase antibodies also underwent a dose-dependent increase (under conditions revealing many immunopositive cells in hypox control animals). The respective increases were 8- to 14-fold for anti-P450scc and P450(17 alpha) and 1.5- to 2-fold for anti-3 beta-hydroxysteroid dehydrogenase. The number of germ cells and the percentage of tubular sections containing late pachytene spermatocytes as most advanced stages of spermatogenesis were subject to similar dose-dependent effects. These results suggest that during puberty PRL stimulates testicular function by promoting multiplication and differentiation of Leydig cells (acting at various steps of steroidogenesis and on tissue responsiveness to LH) and germ cells.

Growth hormone directly affects the function of the different lobes of the rat prostate.

In this study, we investigated the involvement of GH in rat prostate function. First, we demonstrated that specific transcripts corresponding to the GH receptor (4.5 kilobases) and to the GH-binding protein (1.2 kilobases) were expressed in the normal rat prostate, but also in all prostatic carcinoma cell lines tested (LNCaP, PC-3, MAT-Lu, MAT-LyLu, and Pif-1). Moreover, these transcripts were much more abundant in the human and rat carcinoma cells than in the normal tissue. One-year-old dwarf rats were supplemented for 7 days with saline (group DR1) or highly purified rat GH (group DR2). Northern blotting and quantitation of prostatic messenger RNAs (mRNAs) revealed that GH increases the steady state levels of transcripts coding for androgen receptor (2.4-fold), type I and II 5 alpha-reductases (2.6- and 2.2-fold), and several androgen-dependent proteins [prostatein C3 subunit (3.6-fold), probasin (11.0-fold), and R. W. B. (Royal Winnipeg Ballet) (12.5-fold)]. This suggests that GH might either potentiate the action of androgens on the prostate or act directly on this gland by a mechanism that does not depend on testicular androgens. To address this question, we supplemented hypophysectomized and castrated adult rats for 7 days with saline (group HC1), rat GH (group HC2), testosterone propionate (group HC3), or GH plus testosterone (group HC4), starting 3 days after castration. In this animal model, the abundance of C3 mRNA increased in all hormone-treated rats; the stimulation factors were 3.5 (group HC2), 25.5 (group HC3), and 9.5 (group HC4) compared to group HC1. Analysis of prostatein synthesis by Western blotting confirmed these results at the protein level. The same trend was observed for probasin and RWB mRNA levels. Probasin mRNA increased 4.5-fold in group HC2 and 12-fold in group HC3, but did not increase in group HC4 (both hormones combined); enhancement of RWB mRNA was, respectively, 5.0-, 28.0-, and 15.0-fold in groups HC2, HC3, and HC4. GH did not affect the abundance of androgen receptor mRNA. As described previously, the level of this mRNA dropped significantly in group HC3. GH alone did not significantly alter the level of either 5 alpha-reductase mRNA, whereas testosterone, alone or with GH, produced a 2-fold increase in type II 5 alpha-reductase mRNA (groups HC3 and HC4). Type I isoenzyme mRNA reached 1.6 times the control level (group HC1) in groups HC3 and HC4.(ABSTRACT TRUNCATED AT 400 WORDS)

Physiological studies of human chorionic gonadotropin (hCG), alpha hCG, and beta hCG as measured by specific monoclonal immunoradiometric assays.

Several libraries of monoclonal antibodies have been produced against epitopes that reside on hCG, alpha hCG, and beta hCG. Having characterized them physically, we explored their use in the construction of highly specific and sensitive immunoradiometric assays. There were several important immunochemical considerations with respect to developing assays that accurately detect low levels of free subunits in serum in the presence of high concentrations of the native hormone. These include physical properties and specificities of the monoclonal antibodies, choice of capture antibody on the solid phase support, assay design, and purity of hormone standards. Using such assays, we found early pregnancy (in vitro fertilization) to be characterized by the sequential appearance of hCG, followed by beta hCG and then alpha hCG. Molar ratios of beta hCG to alpha hCG and beta hCG to hCG were highest in early gestation. However, there was a reversal of the beta hCG to alpha hCG ratio at 12-13 weeks gestation, and an excess of free alpha hCG was observed thereafter. Except for values obtained in very early pregnancy, the beta hCG to hCG ratio remained remarkably constant at approximately 0.5% throughout gestation. In contrast, choriocarcinoma was distinguished by absolute serum beta hCG concentrations 3-100 times greater than the maximum values observed during pregnancy and, more importantly, by exceedingly high beta hCG to hCG ratios. For comparison, we studied hCG, alpha hCG, and beta hCG levels in an additional 178 patients with nontrophoblastic tumors. Ectopic production of alpha hCG and beta hCG was rare (3%), and thus far, we have been unable to demonstrate the presence of hCG in such patients. Therefore, hCG and the free subunits appear not to be useful as serological markers for nontrophoblastic tumors.

A novel messenger ribonucleic acid homologous to human MAGE-D is strongly expressed in rat Sertoli cells and weakly in Leydig cells and is regulated by follitropin, lutropin, and prolactin.

We have cloned a novel complementary DNA whose expression was decreased in rat Sertoli cell cultures after treatment with FSH. This complementary DNA encodes a protein of 570 amino acids and shares 92% homology with the human MAGE-D protein. In contrast to other MAGE genes (A, B, or C), we have shown that MAGE-D expression was ubiquitous in healthy rat tissues. In the seminiferous tubules, the MAGE-D was expressed in Sertoli cells but not in germ cells as demonstrated by RT-PCR and in situ hybridization, whereas for the other MAGE genes, expression has been shown to be restricted to germ cells. Interestingly, MAGE-D was also detected for the first time in the female gonad by Northern blotting. In MLTC-1 cells (mouse Leydig tumor cell line-1), LH and PRL stimulated MAGE-D expression. Using hypophysectomized rats, it was confirmed that FSH decreased MAGE-D expression, whereas LH and PRL increased MAGE-D messenger RNA level in the whole testis most probably through a direct action on Leydig cells. As MAGE-D is present in both the seminiferous compartment and interstitium and hormonally regulated in each, it is possible that it has specific functions in each compartment during the development and the maintenance of the testis.

A novel gene overexpressed in the prostate of castrated rats: hormonal regulation, relationship to apoptosis and to acquired prostatic cell androgen independence.

We have identified a novel complementary DNA (cDNA) corresponding to a gene overexpressed in the rat ventral prostate after castration. This cDNA displays 89.4% identity with 453 bp of a mouse EST and 81.5% identity with 157 bp of a human EST and was named PARM-1 for prostatic androgen-repressed message-1. The complete cDNA is 1187 bp long and codes for a protein of 298 amino acids that contains four potential glycosylation sites and three half cystinyl residues. The PARM-1 gene was found to be expressed at quite low levels in most rat tissues including those of the urogenital tract. The kinetic of induction of PARM-1 gene in the prostate was highly correlated to the development of apoptosis in the whole organ. Supplementation of castrated animals with androgens reversed both the process of apoptosis and the overexpression of PARM-1 gene. Supplementation with estrogens did not result in an increase in the PARM-1 messenger RNA levels when compared with the castration alone. However, the treatment resulted in a more rapid return to intact levels in the castrated plus estrogen group. When apoptosis of testis and prostate was induced in vivo by hypophysectomy, it was found that PARM-1 was only overexpressed in the prostate. Therefore, PARM-1 seems to be regulated by androgens only in the prostate. Using in situ hybridization and immunohistological techniques, we have shown that PARM-1 gene product is found exclusively in the epithelial cells of involuting prostate. Analysis by flow cytometry of MAT LyLu epithelial cells transiently expressing PARM-1 protein did not allow us to demonstrate a direct effect of PARM-1 gene overexpression on the programmed death of the transfected cells. Treatment of MAT LyLu cells by transforming growth factor-beta induced apoptosis but had no effect on PARM-1 production. However PARM-1 protein has been detected by Western blotting in various cell lines such as MAT LyLu, MAT Lu, and PIF, which are androgen independent. This would suggest that PARM-1 gene product would be a marker for acquired androgen-independence of these tumor cells.

Transient neonatal hyperthyrotropinemia: a factitious syndrome due to the presence of heterophilic antibodies in the plasma of infants and their mothers.

In a national screening program for neonatal hypothyroidism, our criterion for diagnosis is a plasma TSH value exceeding 40 microunits/ml on the fifth day of life. Excluding cases with obvious thyroid abnormalities, we identified a group of 14 neonates with unexplained plasma TSH elevation out of 10,261 screened. The mothers of these infants also exhibited high plasma TSH immunoreactivity; both mother and child in these instances were clinically euthyroid. The material responsible for this TSH immunoreactivity had the following characteristics. After parturition, it disappears from circulation within 2 months in the infants and within 4-6 months in the mother, its apparent molecular weight approximated 150,000 daltons, and its affinity for protein A-Sepharose and its binding properties suggested that the material was an immunoglobulin. Binding is observed typically for heterologous immunoglobulin and human TSH. The heterophilic character of these immunoglobulins explains their interference in many RIA systems, including the TSH RIA commonly used in neonatal screening programs for hypothyroidism.

Follicle-stimulating hormone-secreting pituitary adenomas.

This retrospective study concerns 40 patients with an apparently nonsecretory pituitary adenoma who were operated on during an 11-yr period from 1971 to 1981. Among them, 6 men had elevated serum FSH levels. LH levels were normal in 5 and slightly elevated in 1. Testosterone levels were low in 2 patients and within normal limits in 2 others. Sexual impotency had developed from 6 months to 1 yr before surgery in all patients. Primary hypogonadism could be eliminated on clinical grounds (recent onset of hypogonadism, previous fertility of 5 of the 6, and postoperative improvement). After transsphenoidal adenomectomy, FSH levels returned to normal values in all, and clinical recovery occurred in most patients. Tumor tissue obtained at operation stained positively for the gonadotropins, but was negative for other pituitary hormones in all patients. The most probable explanation for these findings was that the tumors were responsible for the elevated FSH secretion. This explanation is supported by the immunocytochemical identification of gonadotropin-containing cells in the tumors. We conclude that these 6 men from a series of 40 patients who presented with pituitary tumor but no GH, PRL, or ACTH hypersecretion had primary gonadotropinomas.

Early normalization of luteinizing hormone pulsatility after successful transsphenoidal surgery in women with microprolactinomas.

In eight hyperprolactinemic amenorrheic women who had a microprolactinoma, LH secretion was examined by measuring its concentration in blood samples collected every 15 min for 6 h before and 8 days after successful selective adenomectomy. Computer analysis was used for LH peak evaluation. In both circumstances, serum PRL and basal estradiol (E2) levels were also determined. Before operation, the number of LH peaks ranged from zero to one per 6 h in seven patients and was two per 6 h in the eighth patient. In all patients, serum PRL was normal on the eighth postoperative day, while E2 levels remained low, similar to the values usually found in the early follicular phase of the cycle in normal women. Postoperatively, mean LH levels were similar to preoperative levels, but there was a dramatic increase in the number of LH peaks (three to five per 6 h) in five of the eight patients. These observations confirm the impairment of LH pulsatility in hyperprolactinemia and demonstrate that normalization of PRL levels by surgery can restore LH pulsatile secretion in certain women as early as the eighth day after operation in the absence of a significant change in serum E2 levels. Thus, the preoperative impaired pulsatility of LH secretion was probably a central effect of hyperprolactinemia.

Placental and pituitary growth hormone secretion during pregnancy in acromegalic women.

It is now well established that during the second half of normal pregnancy, the human placenta secretes its specific GH variant (placental GH) in increasing amounts up to delivery. During the same period, pituitary GH secretion is progressively suppressed. The present study was aimed at clarifying the physiology of GH secretion in pregnant acromegalic women. Two young women remained acromegalic despite transphenoidal removal of their pituitary adenoma. Increased basal levels of GH and insulin-like growth factor-I (IGF-I) as well as paradoxical GH release after TRH injection were noted. Both women became pregnant and delivered term babies without any complication. In both patients, pituitary GH remained elevated during the entire pregnancy, contrary to the situation in normal women. Paradoxical GH release after TRH treatment was also present, whereas no response was observed in five normal control subjects. GH pulsatility studies revealed a highly pulsatile secretory pattern of pituitary GH, in contrast to that in normal woman, whose placental GH is secreted tonically. Tissue placental GH concentrations were within the range of levels in normal placentas. An increase in serum IGF-I in late pregnancy was also similar to that observed in normal pregnancy. These findings confirm that increased IGF-I levels are not pituitary GH dependent in late pregnancy. They add new evidence that adenomatous somatotrophs lack an IGF-I-dependent feedback regulation present in normal somatotrophs.

Expression of the growth hormone variant gene in human placenta.

Besides the hGH-N gene, which codes for the pituitary 22 and 20K GH variants, the human genome contains a second GH gene, namely the GH-V, which has been thought to be silent. We recently discovered a placental variant of human growth hormone (hPGH), which appears in maternal serum at mid-pregnancy and which rises in concentration thereafter to term. As hPGH and GH-V proteins display very similar characteristics, including a high affinity for hepatic GH receptors, they could be identical. To verify this hypothesis, we sought hGH-V mRNA in placenta. Hybridization experiments were performed between dot-blotted mRNA originating either from placenta or from one pituitary hGH secreting adenoma and synthetic polynucleotide probes corresponding to specific portions of the hGH-V or hGH-N gene sequences. The results indicate that the V gene is indeed expressed in the placenta and, at a very low level, in the pituitary adenoma. Therefore hPGH is most likely the expression product of the hGH-V gene.

Immunocytochemical localization of the human growth hormone variant in the human placenta.

Two monoclonal antibodies (Mab 5B4 and K24) were used for the immunocytochemical localization of human GH (hGH) and human placental GH in the human pituitary and placenta. On the basis of prior selection by RIA, Mab 5B4 was known to be directed to the N-terminal of hGH and was able to detect both pituitary and placental hGH, since their primary amino acid sequences are identical in this domain. Mab K24 was directed to an epitope present in hGH, but not in placental hGH, and was able to detect pituitary hGH only; neither the 5B4 or K24 Mab detected human placental lactogen. Five placentas were studied from women at term after elective cesarean section without labor. The cells of the anterior pituitary gland and the syncytiotrophoblast of the placental villi were stained with Mab 5B4, whereas K24 only stained the pituitary cells; results consistent with the RIA screen. Mab 5B4 specifically stained two different cell types in the placental basal plate. Neither antiserum stained any cell in the amniotic or chorionic membranes or the adherent decidua. The results demonstrate that pituitary hGH and placental hGH are expressed uniquely in the pituitary and fetal placenta, respectively. In addition, the placental hGH gene is also expressed in the placental basal plate, a region of mixed fetal and maternal cells.

The physiology of growth hormones (GHs) in pregnant women and partial characterization of the placental GH variant.

This work was undertaken to study the heterogeneity of GH in serum and placental and pituitary extracts and to study GH physiology in pregnant women. Two distinct monoclonal antihuman GH (anti-hGH) antibodies (MAb) coded 5B4 and K24 were selected for their high binding affinity and specificity. The 5B4 MAb recognized the epitope comprising the NH2-terminal end of hGH, and the K24 MAb recognized an internal epitope. Both MAbs were used in RIAs to measure serum GH concentrations in various circumstances, including pregnancy. The two RIAs yielded slightly different serum GH results in normal men and nonpregnant women, but the overall correlation between the data was excellent. Since the RIAs were not affected by human placental lactogen, the evolution of serum GH in pregnant women could be studied. In such women, serum GH levels progressively declined to undetectable levels during the second half of pregnancy, while a pregnancy-associated serum GH-like antigen [tentatively called human placental growth hormone (PGH)] appeared in the circulation at midpregnancy and increased thereafter up to term. PGH contained the NH2-terminal epitope of pituitary GH, but lacked the internal one. Consequently, it reacted selectively with the 5B4 MAb only. After delivery, PGH disappeared from maternal serum within 1 h. Amniotic fluid contained low GH concentrations; cord serum contained high GH levels, but no PGH. Thus, PGH appears to be secreted selectively into the maternal compartment. PGH was purified from term placenta extracts. According to its chromatographic behavior, it appears more basic than pituitary 22K and 20K GHs. Size dimorphism was demonstrated; PGH was composed of two entities of 22K and 25K, respectively. Pure PGH, obtained in small quantities by preparative electrophoresis, was found to bind to hepatic GH receptor with an apparent high potency compared to that of pituitary GH, PGH, thus, should act in vivo as a GH agonist sharing most of its biological properties. These results lead to the conclusion that PGH is likely to replace the pituitary hormone in governing maternal metabolism during the second half of pregnancy.

Glucose inhibits human placental GH secretion, in vitro.

Human placenta specifically expresses the GH-V gene leading to the production of placental Growth Hormone (PGH). During pregnancy, PGH levels increase progressively in maternal blood, but its regulation remains unknown. In this study the effect of glucose on PGH secretion by human term placenta was tested, in vitro, by means of two different experimental models: organ culture of villous tissue and primary culture of isolated cytotrophoblasts. PGH was assayed in the culture medium by an immunoradiometric assay using a specific PGH monoclonal antibody. The presence of glucose (25 mmol/L) in the culture medium significantly inhibited (p < 0.001) the secretion of PGH by either placental villous explants or by cultured trophoblast cells. This inhibitory effect of glucose on PGH secretion was dose-dependent. More than 50% inhibition being observed with 5.5 mmol/L. In the same conditions, the daily production of hPL and hCG, were unmodified. Furthermore, the glucose-induced inhibition of PGH secretion was more effective when cultured trophoblast cells are differentiated into syncytiotrophoblast. This study demonstrates, for the first time, that among the gestational polypeptide hormones secreted by the human placenta, only PGH secretion is modulated by glucose, suggesting a key metabolic role for this hormone during pregnancy.

Expression of somatostatin receptor SST4 in human placenta and absence of octreotide effect on human placental growth hormone concentration during pregnancy.

In pregnancy, the human placenta GH acts as a growth-promoting hormone and appears to be the main stimulator of insulin-like growth factor I (IGF-I) secretion. In a woman with a TSH-secreting macroadenoma, successful treatment with the somatostatin analog octreotide was conducted during the first month and the second half of pregnancy without side-effects on placental and fetal development. As observed in normal pregnancy, both serum placental GH and IGF-I levels increased throughout pregnancy and dropped sharply after delivery. In placental membranes from both treated and healthy untreated patients, we demonstrated the presence of high affinity binding sites for somatostatin-14 (Kd, 4.6 and 5.3 nmol/L; binding capacity, 1.53 and 1.35 pmol/mg protein, respectively). These receptors displayed low affinity for octreotide (IC50, 1.2-2 mumol/L), suggesting the presence of SST1 and/or SST4 receptors. We found that messenger ribonucleic acids of these two subtypes were expressed in both human placental tissue and purified human cytotrophoblast cells. Finally, the SST1-selective analog, des-AA1,2,5[D-Trp8,IAmp9]S-14 had low affinity for placental somatostatin receptors. These results argue in favor of the presence of the SST4 subtype in human placenta. At the doses administered, octreotide did not bind to placental somatostatin receptors. Our results may explain the absence of changes in both human placental GH and IGF-I concentrations that we observed during octreotide treatment.

Thyrotropin-secreting pituitary adenomas: report of seven cases.

Seven patients with hyperthyroidism due to a TSH-secreting pituitary macroadenoma have been observed of a total of 800 patients with pituitary tumors over a period of 15 yr. Serum TSH levels varied between 1.1-36.3 mU/L. The serum alpha-subunit level was low in 1 case, while in 4 other cases the concentration was elevated and varied between 3.7-7.8 micrograms/L. Serum TSH beta levels were normal in the 4 cases in which it was determined. Serum GH or PRL levels were elevated in 5 cases. In 1 patient the cosecretion of TSH, GH, and PRL was confirmed by immunocytochemical examination. Serum TSH and alpha-subunit responses to TRH, GnRH, CRF, GRF, dexamethasone, methimazole, T3, and bromocriptine administration were variable when studied. Serum TSH and alpha-subunit circadian rhythms were absent in 1 case and inverted in another. A serum alpha-subunit pulsatility without TSH pulses was observed in 1 patient. Five patients underwent transsphenoidal adenomectomy. Three of 4 patients operated on in our center were cured, but a recurrence of the adenoma was found in 1 of them after 5 yr. The fifth patient was not cured. Treatment with octreotide in 3 patients resulted in normalization of serum TSH, GH, and thyroid hormones levels. Cosecretion of PRL in 1 case and alpha-subunit in 2 cases was also inhibited. Partial tachyphylaxis occurred in 1 patient. In summary, heterogeneity in clinical presentation, hormonal expression, and therapeutic response appears to characterize these TSH-secreting adenomas.

Identification of placental human growth hormone as the growth hormone-V gene expression product.

A GH variant of placental origin, placental GH, has recently been shown to replace pituitary GH in maternal serum during pregnancy. Besides, the GH variant (GH-V) gene has been demonstrated to be expressed in the placenta. The similarities between their known properties strongly suggest that the placental GH and the GH-V protein are the same molecular species. Here we provide final evidence that this is indeed the case by sequence analysis of both the 22K and 25K forms. Furthermore, the 25K form is shown to be glycosylated, while the 22K form is not. Both size variants of placental GH are, thus, likely to reflect the partial glycosylation of a unique peptidic chain.

Benign prostatic hyperplasia and normal prostate aging: differences in types I and II 5 alpha-reductase and steroid hormone receptor messenger ribonucleic acid (mRNA) levels, but not in insulin-like growth factor mRNA levels.

Benign prostatic hyperplasia (BPH) is so common in elderly men that the development of adenomatous nodules in this organ can be seen as a normal age-dependent process. In this work, we used Northern blotting to compare the levels of androgen, estrogen, and insulin-like growth factor-I (IGF-I) receptor in young (age range, 23-33; n = 3), old normal (age range, 52-80; n = 3), and BPH-affected subjects (age range, 66-87; n = 15). We have also investigated in these groups the expression of genes coding for the two 5 alpha-reductases (types I and II), aromatase, IGF-I, and IGF-II. Our results show significantly increased levels of IGF mRNA in old healthy and BPH-affected subjects; the respective rises for IGF-I, IGF-II, and IGF-I receptor mRNAs were 3.0-, 2.9-, and 1.5-fold (BPH) and 2.7-, 2.4-, and 1.8-fold (old normal controls). For estrogen receptor, androgen receptor, and type I and II 5 alpha-reductase mRNAs, a marked but opposite effect was observed in adenomatous tissues only; the respective levels were 2.2-, 1.8-, 3.9-, and 1.7-fold lower than those in young adult subjects, whereas no significant differences were recorded between the two normal groups. Morphometric analysis of each tissue specimen confirmed the significantly lower epithelium/stroma ratio in adenomas compared to young or old healthy tissues. Together, these observations suggest that prostatic adenomas may result from at least two conjugate processes: one characterized by a drop in the mRNA levels of steroid hormone receptors, which might be associated with a lower epithelium/stroma ratio, and another characterized by normal aging phenomena, of which the increased production of IGFs and IGF-I receptor transcripts could be biochemical markers.

Perinatal growth hormone (GH) physiology: effect of GH-releasing factor on maternal and fetal secretion of pituitary and placental GH.

To study regulation of the secretion of human pituitary GH (hGH) and placental GH (hPGH) in the pregnant woman and human fetus, the GH-releasing factor Sermorelin [GRF-(1-29)-NH2] was administered to pregnant women at term (n = 5), just before elective cesarean section; saline was administered in control studies (n = 5). The effects of GRF-(1-29)-NH2 administration on maternal and fetal serum concentrations of hGH and GRF-(1-29)-NH2 and maternal serum levels of hPGH were evaluated at birth. The mean time span between injection and birth was 20 min (range, 15-25 min). Cord serum hGH concentrations were similar in infants of GRF-(1-29)-NH2-injected mothers and control infants. GRF-(1-29)-NH2 elicited a consistent but small rise in maternal hGH serum concentrations (P = 0.08), whereas hPGH concentrations remained unaltered. Finally, GRF-(1-29)-NH2 concentrations were undetectable in cord serum, but readily detectable in concomitantly obtained maternal serum. In conclusion, these data suggest that hGH secretion in the pregnant woman at term is suppressed at the pituitary level, that GRF does not affect hPGH secretion, and that fetal hGH secretion is independent of circulating maternal GRF, probably because of lack of transplacental GRF passage.