促性腺激素与骨代谢

新的研究发现骨代谢是受中枢神经系统控制的,脑垂体分泌的促性腺激素刺激破骨细胞的形成和功能,与骨转换和骨量变化密切相关.本文对促性腺激素与骨代谢之间的关系作简要介绍.

Abstract：

New studies have shown that metabolism of bone is controlled by the central nervous system.Gonadotropins secreted by the anterior pituitary stimulate the formation and function of osteoclasts which are closely related to the bone turnover and changes of bone mass. This study overviews the relationship between gonadotropins and bone metabolism.     

生长激素缺乏但持续增高:垂体柄中断合并垂体多激素缺乏一例报告及文献复习

Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.     

生长激素缺乏但持续增高:垂体柄中断合并垂体多激素缺乏一例报告及文献复习

Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.     

生长激素缺乏但持续增高:垂体柄中断合并垂体多激素缺乏一例报告及文献复习

Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.     

生长激素缺乏但持续增高:垂体柄中断合并垂体多激素缺乏一例报告及文献复习

Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.     

生长激素缺乏但持续增高:垂体柄中断合并垂体多激素缺乏一例报告及文献复习

Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.     

生长激素缺乏但持续增高:垂体柄中断合并垂体多激素缺乏一例报告及文献复习

Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.     

生长激素缺乏但持续增高:垂体柄中断合并垂体多激素缺乏一例报告及文献复习

Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.     

生长激素缺乏但持续增高:垂体柄中断合并垂体多激素缺乏一例报告及文献复习

Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.     

生长激素缺乏但持续增高:垂体柄中断合并垂体多激素缺乏一例报告及文献复习

Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.     

Stimulation of longitudinal bone growth by hypophyseal hormones in the hypophysectomized rat.

The stimulating effect of different pituitary hormones on longitudinal bone growth was determined with tetracycline as intravital marker in hypophysectomized rats. Growth hormone was found to be the most effective growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating activity. TSH exerts its effect via the production of thyroxine, whereas the growth stimulation by prolactin seems to be a direct effect of this hormone, similar to the effect of growth hormone. The LH, FSH, ACTH, MSH, vasopressin and oxytocin preparations did not stimulate longitudinal bone growth.     

Molecular aspects of pituitary tumorigenesis

Pituitary tumors, almost invariably adenomas, are of frequent occurrence, accounting for 10% to 15% of all the intracranial neoplasm. They are classified as microadenomas (< 10 mm) or macroadenomas (> 10 mm) and as secreting or clinically non-secreting (or not functioning) adenomas. These tumors are autonomously capable to release pituitary hormones such as the growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The occurrence of metastases, characterizing a pituitary carcinoma, is exceedingly rare. However tumors with aggressive behavior, leading to local invasion, are relatively common. Although the pathogenesis of pituitary tumors is fully characterized, many molecular mechanisms of pituitary tumorigenesis had already been revealed. This review intends to describe advances in the understanding of the involved advances that have been made in the last decade concerning pituitary tumors progression, including the participation of oncogenes, tumor suppressor genes and growth factors.     

Development of radioimmunoassay for bullfrog thyroid-stimulating hormone (TSH): effects of hypothalamic releasing hormones on the release of TSH from the pituitary in vitro

A bullfrog (Rana catesbeiana) thyroid-stimulating hormone (TSH) beta-subunit (TSHbeta) antiserum was produced by employing a C-terminal peptide synthesized on the basis of the amino acid sequence deduced from bullfrog TSHbeta cDNA. Immunohistochemical studies revealed that the bullfrog adenohypophyseal cells that immunologically reacted with the anti-bullfrog TSHbeta corresponded to those positively stained with an antiserum against human (h) TSHbeta. The antiserum was used for the development of a specific and sensitive radioimmunoassay (RIA) for the measurement of bullfrog TSH. The sensitivity of the RIA was 0.75+/-0.07ng TSH/100microl assay buffer. The interassay and intraassay coefficients of variation were 7.6 and 5.3%, respectively. Several dilutions of pituitary homogenates of larval and adult bullfrogs, or medium in which bullfrog pituitary cells were cultured, yielded dose-response curves that were parallel to the standard curve. Bullfrog prolactin, growth hormone, luteinizing hormone, follicle-stimulating hormone, and alpha-subunit derived from glycoprotein hormones did not react in this assay. Immunoassayable TSH in the pituitary culture medium was confirmed to exist in the form of TSHbeta coupled with the alpha-subunit by an immunoprecipitation experiment using the TSHbeta antiserum and an alpha-subunit antiserum. TSH released from pituitary cells into the medium was also confirmed to possess a considerable activity in stimulating the release of thyroxine from the thyroid glands of larval bullfrogs in vitro.The effects of hypothalamic hormones such as mammalian gonadotropin-releasing hormone (mGnRH), ovine corticotropin-releasing hormone (oCRH), and thyrotropin-releasing hormone (TRH) on the release of TSH by dispersed anterior pituitary cells of the bullfrog larvae and adults were also studied. CRH markedly stimulated the release of TSH from both adult and larval pituitary cells. Both TRH and GnRH moderately stimulated the release of TSH from adult pituitary cells but not from the larval cells. This is the first report on the development of an RIA for amphibian TSH, which has provided the direct evidence that the release of TSH from the amphibian pituitary is enhanced by the hypothalamic releasing hormones such as CRH, TRH, and GnRH.     

Current knowledge on the biochemistry and function of hypothalamic hormones

By specialized cell types of the hypothalamus 6 peptides (liberins) acting stimulating on the synthesis and secretion of hormones of the pituitary gland and 3 peptides acting inhibiting (statins) were formed. The synthesis of the hypothalamus hormones apparently takes place from larger precursor molecules. Under influence of corticoliberin the pro-opiomelanocortin is formed in the pituitary gland, the breaking up of which produces in the anterior pituitary lobe the ACTH, the beta-lipotropin and the beta-endorphin as well as in the middle lobe above all melanotropins. The secretion of the growth hormone is furthered above all by the somatoliberin and inhibited by the somatostatin. The luliberin stimulates the secretion of follicle stimulating hormone (FSH) and the luteinising hormone (LH). In increased secretion of prolactin the supply of the FSH- and LH-synthetizing cells with receptors for the luliberin is decreased. The secretion of the prolactin is furthered by the prolactoliberin and inhibited by the prolactostatin. In the regulation of the release of the melanotropins also participate 2 peptides. In the adrenal cortex the melanotropins further the synthesis of glucocorticosteroids stimulated by ACTH.     

Tissue culture studies on human pituitary tumours: long term release of anterior pituitary hormones into the culture medium.

A study was undertaken to determine the length of time that human pituitary tumours are capable of releasing anterior pituitary polypeptide hormones in vitro under basal conditions and to study the spectrum of hormone release by functioning and "non-functioning" pituitary neoplasms. Fragments from the pituitary tumours of 10 patients in the following categories: 1 Cushing's disease, 2 with amenorrhoea-galactorrhoea, 3 with acromegaly, and 4 with "non-functioning" pituitary tumours and from 2 normal human anterior pituitary glands were placed in primary culture immediately after surgery. The in vitro release of human growth hormone (hGH), prolactin (Prl), thyrotrophin (TSH), adrenocorticotrophin (ACTH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) was measured by specific radioimmunoassays at the end of each week in culture. Hormone release was surveyed from 6 weeks to 6 months depending upon the survival of the culture. Hormone release patterns were compared with clinical and pathological data. In the initial week of the study, all 6 anterior pituitary polypeptides were detected in the media from the 2 control pituitaries and from 4 of the tumours (1 amenorrhoea-galactorrhoea and 3 acromegaly) in concentrations up to 100 ng/ml of medium while 5 of the 6 hormones were readily detectable in the media from 2 additional tumour samples (Cushing's disease and 1 "non-functioning" pituitary tumour). The media of the remaining 4 tumours contained at least 3 of the 6 hormones (1 amenorrhoea-galactorrhoea and 3 "non-functioning" pituitary tumours). After 6 months in culture, the 6 hormones were readily detectable in at least 1 of the 5 surviving cultures and hGH (up to 800 ng/ml) and LH were each detectable in the media from 2 cultures. Although most of the hormone concentrations in the media decreased with length of time in culture, there were 2 exceptions. First in the media from 5 of the 12 cultures from both controls and tumours, Prl concentrations increased after 50 to 80 days culture. This increase usually lasted for several weeks before Prl levels again began to decline. The second unusual finding occurred in a tumour from a patient with acromegaly in the media of which hGH levels rose from 60 ng/ml to 800 ng/ml between days 125 and 174. These findings of prolonged hormone release in vitro give promise of future usefulness of tissue culture methods for study of polypeptide hormone releasing mechanisms and long-term production of human anterior pituitary hormones for use in research and possible therapy.     

Prostate-thyroid axis: prostatic TRH is one of the stimulators of thyroid hormone.

Ventral prostatectomy decreased serum thyroid hormones and histology of the thyroid gland indicate that hypothyroid condition. Co-culture of thyroid gland and ventral prostate stimulates thyroid hormone secretion. In the present study we report prostatic thyrotropin releasing hormone (TRH) is the stimulating factor of thyroid hormone secretion. Mature rat (90 days old) ventral prostate, anterior pituitary and thyroid glands were co-cultured in vitro with or without TRH antibody to assess the direct influence ofprostatic TRH on thyroid hormone secretion. Total thyroxine (T4) and triiodothyronine (T3) were increased significantly in the culture media of ventral prostate, anterior pituitary and thyroid gland when compared with thyroid gland plus anterior pituitary culture media. However, media T4 and T3 concentration decreased significantly in thyroid gland alone; also in thyroid gland plus ventral prostate, thyroid gland plus anterior pituitary and thyroid gland plus anterior pituitary plus ventral prostate were co-cultured with TRH antibody (Ab) in a dose dependent manner. The results suggest that ventral prostatic TRH is one ofthe stimulating factors of thyroid hormone secretion under these in vitro conditions.     

Similarity of an estrogen-induced protein and a luteinizing hormone releasing hormone-induced protein

Estradiol induces a 70 kDa protein ('EI70') which is synthesized in vivo in the female rat ventromedial hypothalamus (VMH) and transported to the midbrain central gray, suggesting a role for EI70 in the female mating behavior, lordosis. Luteinizing hormone releasing hormone (LHRH), in addition to stimulating gonadotropin release, potentiates pituitary responsiveness to subsequent exposure to LHRH (the 'priming' effect), facilitates lordosis and induces the synthesis of a 70 kDa protein ('LHRH70') in pituitary in vitro. We now report that EI70 precisely co-migrates on two-dimensional (2-D) gels with the pituitary protein induced by LHRH both in vitro and in vivo. Furthermore, both proteins migrate on 2-D gels in the vicinity of a protein recognized after immunoblotting by antibodies to the heat-shock-70 kDa protein family. The induction of a common protein by estrogen or LHRH could represent a common mechanism by which these hormones facilitate secretion, and by which these hormones interact.     

Cerebrospinal fluid hormone concentration in the evaluation of pituitary tumors.

Cerebrospinal fluid (CSF) concentrations of corticotropin, growth hormone, thyrotropin, prolactin, luteinizing hormone, and follicle stimulating hormone were measured in 28 patients with various neurologic disorders, in 49 patients with pituitary tumors of whom 22 had suprasellar extension, and in 6 patients with craniopharyngiomas. With the exception of 1 patient with pseudotumor cerebri, CSF adenohypophyseal hormone concentrations were low in patients with neurologic disease and in patients with pituitary tumor without suprasellar extension. In marked contrast, 21 to 22 patients with suprasellar extension of a pituitary tumor and 2 of 6 patients with a craniopharyngioma had elevations of one or more CSF adenohypophyseal hormones. Posttreatment CSF adenohypophyseal hormone levels fell from previously elevated levels in 4 of 5 patients. These data suggest that an elevated CSF adenohypophyseal hormone concentration is a sensitive indicator of suprasellar extension of a pituitary tumor, and posttreatment measurements are useful in determining efficacy of therapy.     

The immunocytochemical heterogeneity of silent pituitary adenomas

An immunocytochemical study was performed by the indirect peroxidase method on the pituitary tumour of 37 patients with clinical and biological signs of silent adenoma. Antisera were used against human PRL, human GH, ACTH1-24, human ACTH17-39, alpha-melanocyte stimulating hormone (alpha-MSH), human beta-endorphin, alpha-subunit of hCG (hCG-alpha), and beta-subunits of human LH (LH-beta), human FSH (FSH-beta) and human TSH (TSH-beta). Immunostaining in at least 5% of the tumour cell population, with one or more antisera, was present in 13 cases; hCG-alpha immunostaining was the one most frequently observed. Combined immunostaining was found in 7 cases. Exclusive immunostaining was present in 6 cases: 4 with hCG-alpha, 1 with ACTH1-24 and 1 with TSH-beta. It is concluded that a significant number of silent pituitary adenomas show a certain secretory pattern of pituitary hormones or subunits of glycoprotein hormones as revealed by the immunocytochemistry.     

Enhancement by proopiomelanocortin-derived peptides of growth hormone and prolactin secretion by bullfrog pituitary cells.

Corticotrophs in the bullfrog (Rana catesbeiana) are situated mainly in the rostral region of the anterior lobe of the pituitary gland, which receives its blood supply primarily from the portal vessel. On the assumption that the proopiomelanocortin (POMC)-derived peptides released into the pituitary circulation may influence the function of other pituitary cells situated downstream, the effects of three POMC-derived peptides, namely, N-terminal peptide of POMC (NPP), adrenocorticotropic hormone (ACTH), and joining peptide (JP), on the secretion of growth hormone (GH) and prolactin (PRL) by bullfrog dispersed anterior pituitary cells were examined. NPP and ACTH, but not JP, stimulated the release of GH and PRL in a concentration-dependent manner. It was also found that ACTH1-17, but not alpha-melanocyte-stimulating hormone, was effective in enhancing GH and PRL release. A marked difference between the response to NPP and ACTH and the response to thyrotropin-releasing hormone employed as a reference secretagogue in terms of the time required for stimulating the release of GH and PRL was noted. Northern blot analysis of GH and PRL mRNA levels and radioimmunoassay for GH and PRL in the cultured cells revealed that ACTH increases the syntheses of both pituitary hormones as well. The possibility that NPP and ACTH act on neighboring cells to maintain their overall secretory function is discussed.