Paradoxical elevation of growth hormone by intraventricular somatostatin: possible ultrashort-loop feedback

Somatostatin, the growth hormone-inhibiting factor, when microinjected into the third ventricle of the rat brain, paradoxically induced the release of growth hormone. A pituitary site of action having been ruled out, this result supports the concept that exogenous somatostatin within the hypothalamus acts either to suppress the release of somatostatin from somatostatin-containing neurons, possibly via an ultrashort-loop feedback mechanism, or to augment release of hypothalamic growth hormone-releasing factor, thereby inducing a release of growth hormone. Injection of somatostatin into the third ventricle also decreased plasma concentrations of luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone, probably by inhibiting the release of luteinizing hormone-releasing factor and thyrotropin-releasing factor.     

Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor

There is now evidence that the immune system, during times of infectious challenge, can stimulate the secretion of glucocorticoids, the adrenal steroids that mediate important aspects of the response to stress. Specifically, secretion of interleukin-1 (IL-1), a monocyte lymphokine secreted after infection, appears at least in part responsible for this effect. Glucocorticoids are secreted in response to a neuroendocrine cascade involving, first, the brain, then the pituitary, and finally the adrenal gland. In this report, human IL-1 is shown to activate the adrenocortical axis at the level of the brain, stimulating the release of the controlling hormone corticotropin-releasing factor (CRF) from the hypothalamus. Infusion of IL-1 induced a significant secretion of CRF into the circulation exiting the hypothalamus, whereas immunoneutralization of CRF blocked the stimulatory effect of IL-1 on glucocorticoid secretion. IL-1 appeared to have no acute direct stimulatory effects on the pituitary or adrenal components of this system. Furthermore, IL-1 did not cause a nonspecific release of other hypothalamic hormones. Thus, the lymphokine acts in a specific manner to activate the adrenocortical axis at the level of the brain; this effect appears to be unrelated to the known pyrogenic effects of IL-1 within the hypothalamus.     

Biogenic amines and control of melanophore stimulating hormone release

Release of melanophore stimulating hormone (MSH) from the vertebrate pars intermedia is under inhibitory control by the hypothalamus. Removal of the rat pituitary or the neurointermediate lobe of the frog (Rana pipiens) to in vitro incubation medium results in rapid uninhibited release of MSH. This secretion is inhibited by norepinephrine, epinephrine, phenylephrine, and dopamine, and the inhibition is antagonized by alpha-adrenergic receptor blocking agents. Isoproterenol stimulation of MSH secretion from isolated glands is blocked by pro-pranolol, a beta-adrenergic receptor antagonist. These results implicate dopaminergic or classical alpha-adrenergic receptors (or both) in inhibition of MSH release by catecholamines, and implicate beta-adrenergic receptors in stimulation of MSH release by the bioamines.     

Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary

Somatomedin-C stimulates somatostatin release to a maximum of 390 percent of basal release during short-term (20-minute) incubation of rat hypothalamus. It has no effect on basal or stimulated growth hormone release from primary cultures of rat adenohypophyseal cells during a 4-hour incubation, but inhibits stimulated release by more that 90 percent after 24 hours. These findings suggest that somatomedin-C participates in the growth hormone negative feedback loop with an immediate effect on hypothalamic somatostatin and a delayed effect on the anterior pituitary.     

Release of multiple hormones by a direct action of interleukin-1 on pituitary cells

Exposure to bacterial endotoxins has long been known to stimulate the release of anterior pituitary hormones; administration of endotoxin was at one time a common clinical test of anterior pituitary function. Endotoxin is a potent stimulus for production of the endogenous pyrogenic protein, interleukin-1 (IL-1), by macrophages and monocytes. The possibility that IL-1 has a direct effect on the secretion of hormones by rat pituitary cells in a monolayer culture was investigated. Recombinant human IL-1 beta stimulated the secretion of adrenocorticotropic hormone, luteinizing hormone, growth hormone, and thyroid-stimulating hormone. Increased hormone secretion into culture supernatants was found with IL-1 concentrations ranging from 10(-9) M to 10(-12) M. Prolactin secretion by the monolayers was inhibited by similar doses. These concentrations of IL-1 are within the range reported for IL-1 in serum, suggesting that IL-1 generated peripherally by mononuclear immune cells may act directly on anterior pituitary cells to modulate hormone secretion in vivo. Incubation of IL-1 solutions with antibody to IL-1 neutralized these actions. These pituitary effects of IL-1 suggest that this monokine may be an important regulator of the metabolic adaptations to infectious stressors.     

Melanophore stimulating hormone: release inhibition by ring structures of neurohypophysial hormones

Tocinamide and tocinoic acid, ring structures of oxytocin, are potent inhibitors of the release of melanophore stimulating hormone from the rat and hamster pituitary in vitro. Tocinamide is effective at concentrations as low as 10-(14)M on the mammalian pituitary. These peptides do not affect release of the hormone on the frog (Rana pipiens) pars intermedia, but they do inhibit release in the bullfrog (Rana catesbeiana) and the toad (Bufo marinus). The specificity of the peptides on inhibition of the hormone is demonstrated by the fact that oxytocin, lysine vasopressin, and pressinoic acid and pressinamide (ring structures of the vasopressins) do not show such inhibitory activity. Hypothalamic extracts of either the frog (Rana pipiens) or the rat inhibit release of the hormone from pituitaries of either species. The inhibitory effects of tocinamide and tocinoic acid, like that of hypothalamic extracts, are reversible.     

Prostaglandin involvement in hypothalamic control of gonadotropin and prolactin release

Prostaglandin E(2) (PGE(2)) injected into the third ventricle of ovariectomized rats increased plasma luteinizing hormone dramatically and follicle stimulating hormone slightly. PGE(1) elevated prolactin; PGF(1alpha) or PGF(2alpha) had no effect. PGE(2) or PGE(1) injected directly into the anterior pituitary were ineffective. These results suggest that specific prostaglandins act at the hypothalamus to control pituitary hormone release.     

Kisspeptin在青春期雌性皖西白鹅下丘脑和垂体的定位

运用免疫组化PV-9000二步法和DAB显色技术,研究Kisspeptin在青春期雌性皖西白鹅下丘脑和垂体的定位.免疫组化DAB显色结果表明,在下丘脑后内侧核、室周弓状核和室旁核均可观察到大量Kisspeptin免疫反应阳性神经元,下丘脑室周区及外侧区也可观察到不同程度的Kisspeptin阳性细胞;腺垂体中亦可见少量免疫阳性产物,但神经垂体无阳性细胞.Kisspeptin在雌性青春期皖西白鹅下丘脑和垂体中均有分布,初步揭示Kisspeptin在调节促性腺激素的分泌和参与生殖调控以及青春期的启动中均具有非常重要的作用.     

Vasopressin and neurophysin: high concentrations in monkey hypophyseal portal blood

Vasopressin and its binding protein, neurophysin, were measured by radioimmunoassay in the hypophyseal portal blood of monkeys after cannulation of individual long portal veins. Mean vasopressin concentrations (13,800 picograms per milliliter) in portal blood were more than 300 times as high as those in the systemic circulation (42 picograms per milliliter). Neurophysin concentration was approximately 25 times as high in portal as in systemic blood. By immunoperoxidase techniques, high concentrations of neurophysin were demonstrated around portal capillaries of the median eminence. These studies indicate direct secretion of vasopressin and neurophysin into the portal circulation; the quantities secreted during stress may be sufficient to exert significant effects on secretion of anterior pituitary hormone.     

Luteinizing hormone-releasing activity in hypophysial stalk blood and elevation by dopamine

Pituitary halves incubated in pituitary stalk plasma release more luteinizing hormone than their opposite halves incubated in plasma from peripheral blood. Glands incubated in stalk plasma from dopamine-treated rats release more luteinizing hormone than glands incubated in stalk plasma from untreated controls. Luteinizing hormone-releasing activity in stalk plasma may be due to the luteinizing hormone-releasing factor, and the secretion of luteinizing hormone-releasing factor may be controlled by a dopaminergic mechanism.     

Corticotropin-releasing activity of monokines

Hepatocyte-stimulating factor and interleukin-1 are proteins produced by monocytes in response to inflammatory challenge. Neither of these monokines had direct effects on steroid production by cultured adrenocortical cells. Both monokines stimulated pituitary cells (AtT-20) to release adrenocorticotropic hormone; interleukin-1 was equipotent with a combination of corticotropin-releasing factor and arginine vasopressin, and hepatocyte-stimulating factor was at least three times as effective. The synthetic glucocorticoid, dexamethasone, inhibited production of hepatocyte-stimulating factor by cultured monocytes. These results indicate an axis between monocytes and pituitary and adrenocortical cells which may play a role in regulating host defense.     

Stimulation of gonadotropin release by a non-GnRH peptide sequence of the GnRH precursor

The human gonadotropin-releasing hormone (GnRH) precursor comprises the GnRH sequence followed by an extension of 59 amino acids. Basic amino acid residues in the carboxyl terminal extension may represent sites of processing to biologically active peptides. A synthetic peptide comprising the first 13 amino acids (H X Asp-Ala-Glu-Asn-Leu-Ile-Asp-Ser-Phe-Gln-Glu-Ile-Val X OH) of the 59-amino acid peptide was found to stimulate the release of gonadotropic hormones from human and baboon anterior pituitary cells in culture. The peptide did not affect thyrotropin or prolactin secretion. A GnRH antagonist did not inhibit gonadotropin stimulation by the peptide, and the peptide did not compete with GnRH for GnRH pituitary receptors, indicating that the action of the peptide is independent of the GnRH receptor. The GnRH precursor contains two distinct peptide sequences capable of stimulating gonadotropin release from human and baboon pituitary cells.     

Endothelin stimulation of cytosolic calcium and gonadotropin secretion in anterior pituitary cells

The presence of endothelin, a vasoconstrictor peptide, in the hypothalamus and posterior pituitary suggests that it also regulates neural and other nonvascular target cells. In pituitary gonadotrophs, low doses of endothelin evoked oscillations in the intracellular calcium concentration, and high doses induced a biphasic calcium response. Mobilization of intracellular calcium predominated during the spike phase of the calcium response to endothelin, whereas calcium entry through dihydropyridine-sensitive channels contributed to both the spike and plateau phases of the calcium response. Endothelin was a potent as hypothalamic gonadotropin-releasing hormone (GnRH) in stimulation of gonadotropin release in perifused pituitary cells. Endothelin bound specifically to pituitary cells with a dissociation constant of 70 picomolar, and induced rapid formation of inositol trisphosphate and diacyglycerol. Although intracellular calcium concentration and gonadotropin secretory responses to endothelin were independent to the GnRH receptor, endothelin and GnRH appeared to have a common signal transduction mechanism. These observations suggest that endothelin can act as a neuropeptide to regulate anterior pituitary function.     

猪NPY受体Y1 cDNA的克隆及分析

[目的]研究猪NPY-Y1受体在猪激素分泌及发育生理功能中的调节作用。[方法]从初情期的苏姜猪母猪中提取下丘脑组织总RNA,RT-PCR扩增出NPY-Y1 cDNA,扩增产物克隆入pGEM-T easy载体中进行序列测定。[结果]试验扩增产物与GeneBank公布的猪NPY-Y1序列比较,其同源性达到100%。[结论]为下一步研究猪NPY-Y1基因的生理功能和作用机理奠定了基础。     

Nesfatin-1对初情期雌性大鼠促性腺激素及其mRNA表达的影响

为探究侧脑室注射Nesfatin-1对雌性大鼠促性腺激素水平及其mRNA表达的影响,对初情期前雌性大鼠的侧脑室注射Nesfatin-1,采用实时荧光定量PCR法检测促黄体素(Luteinizing hormone,LH)和促卵泡素(Folliclestimulating hormone,FSH)mRNA在垂体中的变化,采用酶联免疫分析法检测血清LH和FSH的浓度。结果表明:在初情期前的雌性大鼠中,Nesfatin-1可促进初情期启动、增加卵巢重量、血清LH水平、垂体LH mRNA和FSH mRNA的表达增加(P0.05);但Nesfatin-1对FSH水平的影响不突出,注射后15min时增加(P0.05),60min不产生影响(P0.05)。侧脑室注射Nesfatin-1后15和60min均能提高血清LH水平,15min时提高更明显(P0.05),但对FSH水平的影响不尽相同。在成年的雌性大鼠中,Nesfatin-1对LH和FSH的分泌不产生影响(P0.05)。Nesfatin-1可通过下丘脑诱导和增强初情期过渡阶段雌性大鼠LH和FSH的释放及LH、FSH mRNA的表达。     

Control of the rhesus monkey menstrual cycle: permissive role of hypothalamic gonadotropin-releasing hormone

In rhesus monkeys with hypothalamic lesions (which appear to abolish the endogenous production of gonadotropin-releasing hormone), normal ovulatory mestrual cycles were reestablished by an unvarying, long-term replacement regimen consisting of one intravenous pulse of synthetic gonadotropic-releasing hormone per hour. This finding is in accord with the hypothesis that the pattern of pituitary gonadotropin secretion throughout the menstrual cycle (basal secretion interrupted, once every 28 days on the average, by a preovulatory surge) is not directed by alterations in hypothalamic gonadotropin-releasing hormone secretion but by the ebb and flow of ovarian estrogens acting directly on the pituitary gland.     

Pheromone-induced changes in the acidophil concentration of mouse pituitary glands

Pituitaries of female mice in anestrus resulting from colony housing were characterized by a 58.0-percent (acidophil content. Subsequent exposure to restrained male mice for one and two nights failed to evoke significant acidophilic degranulation and resulted in pituitary acidophil values of 57.4 and 55.1 percent respectively. Exposure to released males on the third night produced marked acidophilic degranulation resulting in a significant decline in pituitary acidophils to 38.0 percent. These findings support the view that female pheromone suppresses and male pheromone favors the secretion of follicle-stimulating hormone and indicate that luteotrophic hormone is secreted at its assigned time in the sequence of cyclic ovarian events initiated by the secretion of follicle-stimulating hormone.     

VIP基因在狮头鹅繁殖周期下丘脑-垂体-性腺轴中的表达变化

为了探索狮头鹅繁殖周期下丘脑-垂体-性腺轴中VIP mRNA的表达规律,选取产蛋期、就巢期、休产期狮头鹅母鹅各6只,采用荧光定量PCR方法分别测定了各时期下丘脑、垂体及卵巢VIP mRNA的表达水平。结果表明,狮头鹅就巢期血清催乳素(PRL)质量浓度为30ng/mL,明显高于产蛋期和休产期(P<0.01),下丘脑就巢期VIP mRNA的表达量较其他繁殖周期高(P<0.05),而垂体产蛋期VIP mRNA的表达量最高(P<0.01)。提示狮头鹅下丘脑-垂体-性腺轴中VIP mRNA的表达水平与PRL分泌密切相关,PRL是狮头鹅就巢行为维持和发展的关键激素。