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Pathology of the pituitary gland in patients with the acquired immune deficiency syndrome (AIDS).

The pituitary gland was examined at autopsy in 88 patients who died with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC). Pathologic findings included focal to widespread necrosis and/or fibrosis of the anterior pituitary gland in 10 cases, evidence of cytomegalovirus infection without an apparent inflammatory component in the anterior pituitary in 3 cases, and microglial nodules in the pars nervosa in 5 cases. In one instance, a multinucleated giant cell identical to those associated with direct human immunodeficiency virus infection of brain was identified in the pars nervosa. One patient showed focal anterior pituitary infection by Cryptococcus neoformans in the context of widespread and severe cryptococcosis. These findings are discussed in relation to the possible clinical manifestations and the neuropathologic and systemic pathologic findings in AIDS patients.

AIDS-Related Complex↗

Effects of in vivo pretreatment with D-Trp-6-LH-RH on prolactin and LH secretion by pituitary glands in vitro.

In order to study a possible direct action of LH-RH analogs on the pituitary lactotrophs, we investigated the effect of long-term in vivo pretreatment with D-Trp-6-LH-RH on in vitro secretion of PRL and luteinizing hormone (LH) by the pituitary glands from male and female rats. In vivo pretreatment with D-Trp-6-LH-RH (50 micrograms/day, SC) for 15 days greatly reduced basal in vitro PRL release (p less than 0.01) in female, but not in male pituitary glands. TRH-stimulated PRL secretion was not affected by pretreatment with D-Trp-6-LH-RH in female rats, but was impaired in male pituitaries. Acute in vitro exposure to D-Trp-6-LH-RH did not modify PRL secretion by female pituitary glands pretreated in vivo with the analog. However, this same in vivo pretreatment greatly decreased PRL release from male pituitaries (p less than 0.01). Basal in vitro LH release by male pituitary glands was partially lowered by in vivo pretreatment with D-Trp-6-LH-RH, as compared to controls (p less than 0.01), while basal LH release in female pituitaries remained at control levels. Finally, D-Trp-6-LH-RH-induced stimulation of in vitro LH release was severely impaired in female pituitaries (p less than 0.01) but only slightly reduced in the males.

Animals↗

Correlation between LH secretion in castrated rats with cellular proliferation and synthesis of DNA in the anterior pituitary gland.

The relationship between the release of LH and the synthesis of DNA was studied in the anterior pituitary gland of castrated rats. Cell types were characterized immunocytochemically. Castration significantly (P less than 0.01) increased the concentration of LH in serum (1326%) and the incorporation of [3H]thymidine into pituitary DNA (72%). This was accompanied by an increment in the activity of the enzyme DNA polymerase-alpha (58%) and in the number of mitoses (from 2 +/- 0.1/mm2 in intact rats to 21 +/- 0.8/mm2 15 days after castration). Only 20% of the mitoses found in the pituitary gland of castrated rats were positively stained with the antiserum against the beta-subunit of LH. The other 80% did not stain either with LH antiserum or with antisera against the other pituitary hormones. There was a significant (P less than 0.01) increase in the number of LH cells in castrated rats (48%). All the changes produced in the anterior pituitary gland after castration were prevented by the administration of dihydrotestosterone. The results demonstrate that a stimulation of LH release is followed by an increase of DNA synthesis and cell proliferation of gonadotrophs in the anterior pituitary gland.

Animals↗

Differential distribution of melatonin receptors in the pituitary gland of Xenopus laevis.

A major target site for melatonin action is thought to be the pituitary gland. We have detected differential expression and co-localization of the Mel(1a) and Mel(1c) receptors in cells of the Xenopus laevis pituitary gland. Sections of Xenopus pituitary glands were labeled with Mel(1a) and/or Mel(1c) antibodies, in combination with antibodies to arginine vasotocin (AVT), alpha-melanocyte stimulating hormone (alpha-MSH), prolactin (PRL), and luteinizing hormone (LH). Mel(1a) immunoreactivity was localized to cells of the pars intermedia and to elements within the pars nervosa. Mel(1c) immunoreactivity was also localized to the pars nervosa, and significant labeling was also observed in discrete clusters of cells in the pars distalis. Mel(1a) was absent from the pars distalis, while Mel(1c) was absent from the pars intermedia. Mel(1a) and Mel(1c) were co-localized in the pars nervosa. AVT was present in the pars nervosa, and appeared to be localized to the cell clusters of the pars distalis in which the Mel(1c) receptor was localized. alpha-MSH co-localized with the Mel(1a) receptor in the pars intermedia. LH appeared to localize to many of the cells in the pars distalis, with the notable exception of the Mel(1c) receptor-positive clusters of cells. PRL did not appear to co-localize with either melatonin receptor. The pattern of differential expression of the Mel(1a) and Mel(1c) receptors suggests that the receptors specifically mediate the cellular response to melatonin binding in the specific cell populations.

Animals↗

Trace elements in Alzheimer's disease pituitary glands.

Levels of mercury (Hg), selenium (Se), iron (Fe), rubidium (Rb), and zinc (Zn) were measured in the pituitary gland to assess the possibility of a potential difference in the environmental Hg exposure of Alzheimer's disease (AD) patients and control subjects and levels of other elements of interest in AD. The pituitary gland has been established as a good predictor of environmental Hg exposure. Neutron activation analysis was utilized to determine levels of these elements in pituitary glands of 43 AD subjects and 15 control subjects. No significant differences were observed between the AD and control means for these five elements. The sole significant Pearson's correlation involving Hg was the established correlation with Se, indicative of the detoxification of Hg. The absence of a statistical difference between AD and control pituitary gland Hg levels suggests AD patients do not have an excessive environmental exposure to Hg compared to controls.

Aged↗

[Qualitative and quantitative changes of luteinizing hormone (LH) in the pituitary glands in female Japanese monkeys (Macaca fuscata) during the menstrual cycle and after castration].

The present study was designed to investigate qualitative and quantitative changes in luteinizing hormone (LH) in the pituitary glands of female Japanese monkeys (Macaca fuscata) during the menstrual cycle and after castration. The pituitary glands were removed from 10 intact cycling Japanese monkeys and 3 castrated ones: The former sacrificed in the early, late follicular phase, and mid luteal phase, and the latter 8 weeks after castration. All 13 pituitary glands were fractionated by isoelectrofocusing (IEF). The mid cycle peaks of estradiol (E2) and bioactive LH occurred simultaneously in 11 out of 13 monkeys. No animals showed luteal phase peaks in the plasma E2 concentration. Bioactive LH content (IU/mg wet weight) in the pituitary gland was significantly correlated with plasma E2 levels in the cycling monkeys (R2 = 0.974) and it was the highest in monkeys in the late follicular phase. Bioactive LH in the pituitary gland was separated into 6 distinct species in terms of pI values by IEF; A(9.31 +/- 0.19), B(8.88 +/- 0.17), C(8.36 +/- 0.17), D(7.92 +/- 0.18), E(7.32 +/- 0.16) and F(acidic LH). Among alkaline LH species, the most predominant ones were Fractions B, C and D in the early follicular phase, Fraction A followed by B in the late follicular phase and Fraction B followed by C in the mid luteal phase. The neutral and acidic LH (Fraction E and F) was increased more in the early follicular phase and in the castrates. In conclusion, LH species separated by IEF may correspond to the stage of molecular maturation of pituitary LH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Human fetal pituitary gland in holoprosencephaly and anencephaly.

The normal prenatal development of the human pituitary gland and the gland-supporting sella turcica has recently been investigated. The sella turcica area constitutes a developmental boundary area in the cranial base. Posterior to the area the cranial base has developed close to the notochord, and anterior to the region the cranial base development is dependent chiefly on neural crest cell migrations. In the present study the sella turcica region was analyzed in two fetuses with holoprosencephaly (cyclopia and median cleft) and four fetuses with anencephaly combined with rachischisis in the neck region (GA 16-20 weeks). The sella turcica region was investigated radiologically and histologically. Adenohypohyseal gland tissue was localized by immunohistochemical hormonal marking. In both types of malformation an open craniopharyngeal canal was seen in the base of the sella turcica with adenohypophyseal glandular tissue located in the sella turcica, in the canal, and in the pharyngeal connective tissue at the external side of the cranial base. In conclusion, severe malformations of the pituitary gland occur in both holoprosencephaly, which is a polytopic field defect located anterior to the sella turcica, and in anencephaly associated with notochordal insufficiency posterior to the sella turcica. This might indicate that the sella turcica area, bounding different developmental fields, is involved in various craniofacial malformations. It is consequently recommended that examination of the pituitary gland should become a part of the routine autopsy of prenatal material when malformations in the face, brain, and cranial base occur.

Anencephaly↗

Nucleolar organizer regions in pituitary gland adenomas.

Nucleolar organizer regions are DNA segments concerned with the synthesis of ribosomal RNA (rRNA). Some specific proteins related to NORs can be demonstrated by a silver technique and are then referred to as Ag-NORs. The mean number of Ag-NORs per cell has been used as a marker of cell proliferation in recent years and there is some evidence to suggest that Ag-NOR counts can be used to differentiate between normal and neoplastic cells. Paraffin block sections of 42 pituitary gland adenomas and 24 normal adult pituitary glands have been examined using the Ag-NOR staining technique. Touch imprints of nine adenomas and 12 normal adult pituitary glands were also examined using the same Ag-NOR staining technique. Using light microscopy at x2000 magnification, the Ag-NORs were located as black dots in the cell nuclei and the mean number of Ag-NORs per cell was determined. No significant difference was observed between blocked sections and imprints of adenomas or between imprints and paraffin sections of normal glands. However, a significant difference was observed between the mean number of Ag-NORs in pituitary gland adenomas and normal glands in paraffin block sections and touch preparations (P less than 0.001). The modified Ag-NOR technique can be a useful aid in the differential diagnosis between normal pituitary gland tissue and pituitary adenomas, especially during surgical operations.

Adenoma↗

Regulation of the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in the rat anterior pituitary gland.

TRH-like peptides share the N- and C-terminal amino acids with TRH (pGlu-His-Pro-NH2) but differ in the middle amino acid residue. One of them, pGlu-Glu-Pro-NH2 (< EEP-NH2; EEP) is present in the rat pituitary gland, but its biological significance is unknown. We investigated the localization and regulation of this tripeptide in the rat pituitary gland. To distinguish between TRH and EEP two antisera were used for RIA: specificity of antiserum 4319 for the TRH-like peptides pGlu-Phe-Pro-NH2 and EEP was equal to or greater than that for TRH, whereas antiserum 8880 is TRH-specific. Our RIA data showed the presence of a TRH-like peptide in the anterior pituitary gland (AP) and of TRH in the posterior pituitary gland (PP). The TRH-like peptide in the AP was identified on anion-exchange chromatography and subsequent HPLC as EEP. Pathophysiological conditions such as altered thyroid and adrenal status and suckling did not affect pituitary gland levels of EEP. In general, however, there is a clear sex difference: levels of EEP are higher in male than in female rats. In both sexes gonadectomy leads to a substantial two- to threefold rise in EEP levels, abolishing the sex difference. Testosterone administration to gonadectomized male rats normalizes levels of EEP again. Disulfiram, an inhibitor of the enzyme peptidylglycine alpha-amidating monooxygenase, reduced levels of EEP in the AP by approximately 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Luteinizing hormone secretion by dispersed anterior pituitary gland cells from middle-aged rats.

Several studies have shown that a certain subpopulation of middle-aged rats have an attenuated preovulatory LH surge, and that this is an early indicator of a general decline in reproductive cyclicity. The pituitary glands of middle-aged animals with attenuated LH surges have been shown to be significantly less responsive to GnRH than those from young (Y) animals. The present study was designed to investigate the relationship between the in vivo LH surge and the in vitro secretory capacity of dispersed anterior pituitary gland cells from the same animals. Individual LH-secreting cells were also studied with respect to their LH secretory capacity and proportionate numbers in the pituitary gland using reverse hemolytic plaque assay (RHPA). Two groups of animals, young (4-5 months old) and middle-aged (10-12 months old), were sampled on the afternoon of proestrus to determine the amplitudes of their preovulatory LH surges. The middle-aged animals were then classified as either normal (MAN) or attenuated (MAA) with regard to the peak levels of the surges. On the next proestrus, dispersed anterior pituitary gland cells were prepared for either perifusion or RHPA. Perifused anterior pituitary gland cells were exposed to three 2.5-min pulses of GnRH(30 nM) at 60-min intervals. In the RHPA, red blood cells were treated with protein-A to allow coating with rabbit antiovine LH-beta, and then co-incubated with anterior pituitary gland cells. The cells were then treated with one of several concentrations of GnRH (0.01, 1.0, 10, or 100 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

An autoradiographical study of binding sites for vasopressin located on corticotrophs in rat and sheep pituitary glands.

Arginine vasopressin (AVP) carried by hypophysial portal blood acts in the pituitary gland, in synergy with corticotrophin-releasing factor (CRF), to induce ACTH secretion. The relative importance of AVP and CRF in this secretory response depends upon the nature and intensity of stressful stimuli, and perhaps also on the species. The aim of the present work was to study, in isolated rat and sheep pituitary glands, the topography of binding sites for AVP and to establish whether they are indeed associated with corticotrophs. To this end, we performed contact autoradiography on tritium-sensitive film using 1.5-2.0 nmol [3H]AVP/l as ligand. ACTH immunoreactivity was detected on sections immediately adjacent to those used for autoradiography. In both species, specific binding sites for AVP were only present in the anterior lobe; the intermediate lobe was not labelled and the neural lobe showed non-specific labelling. Autoradiograms from experiments using [3H]AVP in competition with different synthetic structural analogues showed that, in rat and sheep anterior pituitary glands, receptors differ from the V1 and V2 subtypes. Specific [3H]AVP-binding sites formed an irregular, patchy pattern throughout the anterior lobe. In both species, this pattern was strikingly similar to that formed by cell clusters showing ACTH immunoreactivity, indicating that the AVP-binding sites are associated with the corticotrophs. Immunoreactive cells in the intermediate lobe had no [3H]AVP-binding sites. [3H]AVP binding was more intense in the sheep than in the rat anterior lobe, suggesting that AVP may be particularly important for ACTH secretion in the sheep.

Adrenocorticotropic Hormone↗

Ultrastructural evidence for endogenous substance-P-like immunoreactivity in the rat pituitary gland.

Substance P (SP) is known to act on pituitary hormone release either at the hypothalamic level or directly at the pituitary level. In order to investigate whether SP is present in the pituitary gland and to localize the peptide at the cellular and subcellular levels, the immunocytological method was used. Rat pituitaries were fixed and frozen. Ultrathin sections, obtained by cryoultramicrotomy, were incubated with anti-SP serum. The antigen-antibody reaction was detected by 4-chloro-1-naphtol. SP immunoreactivity was observed both in the prolactin and in the gonadotropic cells, but not in the somatotropic, corticotropic and thyrotropic cells. In reactive cells, SP immunoreactivity was observed in the secretory granules, in the cytoplasm, and in the nucleus distributed all over the euchromatin near to the heterochromatin regions. No immunoreactivity was observed when nonimmune serum or anti-SP serum incubated with SP was used. No modification of the immunocytochemical reaction was observed when anti-SP serum incubated with somatostatin, gonado- or thyroliberin was used. These data (1) provide immunocytological evidence for the presence of SP in the pituitary gland; (2) indicate the presence of SP peptide in the gonadotropic and prolactin cells only. They support previous findings indicating that SP could have a direct effect at the pituitary level.

Animals↗

WNT5A signaling affects pituitary gland shape.

Wnt signaling is important in organogenesis, and aberrant signaling in mature cells is associated with tumorigenesis. Several members of the Wnt family of signaling molecules are expressed in the developing pituitary gland. Wnt5a is expressed in the neuroectoderm that induces pituitary gland development and has been proposed to influence pituitary cell specification. We discovered that mice deficient in Wnt5a display abnormal morphology in the dorsal part of the developing pituitary. The expression of downstream effectors of the canonical Wnt pathway is not altered, and expression of genes in other signaling pathways such as Shh, Fgf8, Fgf10 and Fgfr2b is intact. Prop1 and Hesx1 are also important for normal shape of the pituitary primordium, but their expression is unaltered in the Wnt5a mutants. Specification of the hormone-producing cell types of the mature anterior pituitary gland occurs appropriately. This study suggests that the primary role of Wnt5a in the developing pituitary gland is in establishment of the shape of the gland.

Animals↗

Endothelin in human brain and pituitary gland: presence of immunoreactive endothelin, endothelin messenger ribonucleic acid, and endothelin receptors.

The presence of immunoreactive (IR) endothelin, endothelin mRNA, and endothelin receptors in human brain and pituitary gland has been studied by RIA, Northern blot hybridization, and receptor assay. IR endothelin was detected in all five brain regions examined (cerebral cortex, cerebellum, brain stem, basal ganglia, and hypothalamus) (6-10 fmol/g wet wt) and spinal cord (22 +/- 6 fmol/g wet wt, n = 7, mean +/- SEM). Higher concentrations of IR endothelin were found in the pituitary gland (147 +/- 30 fmol/g wet wt). Fast protein liquid chromatographic analysis of the IR endothelin in pituitary gland showed a large IR peak in the position of endothelin-3 and a smaller peak in the position of endothelin-1, whereas IR endothelin in the hypothalamus and brain stem was mainly endothelin-1. Endothelin messenger RNA was detected by Northern blot hybridization in the pituitary but not in hypothalamus. The receptor assay showed that 125I-endothelin-1 binding sites were present in large numbers in all five brain regions but were much less abundant in the pituitary gland. Binding capacity and dissociation constant were 5052 +/- 740 fmol/mg protein and 0.045 +/- 0.007 nM in brain stem and 963 +/- 181 fmol/mg protein and 0.034 +/- 0.009 nM in hypothalamus. In the pituitary gland, there were two classes of binding sites for endothelin with dissociation constants of 0.059 +/- 0.002 nM (binding capacity = 418 +/- 63 fmol/mg protein) and 0.652 +/- 0.103 nM (binding capacity = 1717 +/- 200 fmol/mg protein). Endothelin-1, -2 and -3 were almost equipotent in displacing the binding (IC50 approximately 0.04 nM). These findings are in accord with the possibility that endothelin acts as a neurotransmitter, neuromodulator or neurohormone in man.

Aged↗

Immunocytochemical demonstration of CB1 cannabinoid receptors in the anterior lobe of the pituitary gland.

Both exogenous and endogenous cannabinoids can influence hormone secretion from the anterior pituitary gland. A large body of information proves that the primary target of these effects is the neuroendocrine hypothalamus. However, recent studies using cannabinoid (CB) receptor autoradiography, messenger RNA in-situ hybridization and in-vitro analysis, indicate direct effects of cannabinoids at the level of the anterior pituitary gland itself. In the present paper, the immunocytochemical distribution of CB in the adult rat anterior pituitary was studied using specific polyclonal antibodies against CB1 (central) and CB2 (peripheral) receptors. Due to its resolution, this method allowed identification of individual anterior pituitary cells possessing cannabinoid receptors. The specific hormone immunoreactive cells with receptor-like immunoreactivity were compared on adjacent sections. CB1-like immunoreactivity (CB1ir) was found in the lactotroph cells as well as in luteinizing hormone (LH) secreting gonadotrophs. The CB1ir positive material present in the cytoplasm of these cells was less homogeneous than the hormone immunoreactive material, and it was also seen at the periphery of the cells, presumably on the cell membrane. No CB1ir was found in growth hormone (GH) secreting cells and it was hardly seen in the corticotrophs. No CB1ir was detected in the posterior pituitary. CB2ir was not observed in any part of the pituitary gland. The results support the view that the site of action of cannabinoids on neuroendocrine regulatory mechanisms may be both at pituitary and hypothalamic levels. We suggest that at least the direct effect of cannabinoids on the regulation of LH and prolactin secretion is mediated via CB1 cannabinoid receptors in the anterior pituitary.

Animals↗

Neuron-specific enolase in the pituitary gland.

Neuron-specific enolase (NSE) is present in many types of peptide-secreting neuroendocrine cells and in tumours derived from them, but little work has been done on the pituitary gland. Serial sections of normal rat (n = 9) and human (n = 7) pituitary gland, spontaneous rat pituitary tumours (n = 14) and human pituitary tumours, both hormonally active (n = 7) and inactive (n = 10), were immunostained for NSE and the 6 major anterior pituitary hormones. The neural lobe stained strongly and the intermediate lobe variably for NSE. In the anterior lobe, NSE immunoreactivity was present with variable intensity in the majority of hormone-producing cells of all six types. Cells with strong hormone immunoreactivity were usually only moderately stained for NSE. All the human and rat pituitary adenomas examined were positively stained for NSE, though to varying degrees. The pituitary gland is thus no exception to the rule that NSE is found in peptide-secreting neuroendocrine cells and their tumours.

Acromegaly↗

Leu-Phe cleaving endopeptidase activity, gamma-endorphin, and beta-endorphin in the rat pituitary gland and brain. Effect of adrenalectomy and corticosterone substitution.

The influence of adrenalectomy and corticosterone substitution was investigated on Leu-Phe cleaving endopeptidase activity and on the levels of gamma-endorphin and beta-endorphin in the pituitary gland and the brain. The enzyme activity was quantitated by a specific radiometric assay based on the cleavage of the Leu17-Phe18 bond in a NH2- and COOH-terminally protected synthetic substrate which was analogous to beta-endorphin-(15-19). This activity may mimick the formation of gamma-endorphin. beta-Endorphin and gamma-endorphin were measured by specific radioimmunoassays. After 14 days of adrenalectomy enzyme activity had increased in anterior (15%) and neurointermediate lobes of the pituitary gland (30%), hypothalamus (25%), and liver (15%). This increase was prevented when the adrenalectomized animals were subjected to chronic corticosterone substitution by subcutaneous implantation of a pellet of 100 mg. Extirpation of only the adrenal medulla did not affect the Leu-Phe cleaving activity. Enzyme activity in the septum, hippocampus, and cerebellum had not changed after adrenalectomy. Determination of immunoreactive levels of gamma- and beta-endorphins showed that in the anterior pituitary gland gamma- and beta-endorphins had increased by 275 and 300%, respectively, 14 days after adrenalectomy. No significant changes were observed in endorphin levels of the intermediate lobe of the pituitary gland, hypothalamus, hippocampus, and septum. The results indicate that Leu-Phe cleaving endopeptidase activity in sensitive to glucocorticoids in tissues containing proopiomelanocortin-producing cells, i.e., anterior and neurointermediate pituitary gland and the hypothalamus. In the anterior pituitary gland it is correlated with the levels of gamma- and beta-endorphins.

Adrenalectomy↗

Estrogen alters the responsiveness of the anterior pituitary gland to the actions of dopamine on lysosomal enzyme activity and prolactin release.

The effects of dopamine on PRL secretion and lysosomal enzyme activity in anterior pituitary tissue from rats selected during various stages of the estrous cycle were examined under in vitro conditions. During the estrous cycle, there was a marked variation in the capacity of dopamine to stimulate the activity of the lysosomal enzyme beta-glucuronidase in the anterior pituitary gland. Moreover, this variation in the responsiveness of pituitary tissue to the stimulatory action of dopamine on beta-glucuronidase activity was accompanied by a similar variation in the responsiveness of the tissue to the inhibitory action of dopamine on PRL release. Anterior pituitary glands from diestrous rats were the most sensitive to the actions of dopamine on beta-glucuronidase activity and PRL release, whereas glands from estrous animals were the least sensitive. Ovariectomy on the day of diestrus prevented the decline in the responsiveness of the anterior lobe to the actions of dopamine normally seen 2 days later (on the presumptive day of estrus). On the other hand, when animals were treated with estradiol benzoate during the 2 days after ovariectomy, the responsiveness of the pituitary tissue to dopamine was markedly suppressed and was similar to that of tissue from estrous rats. When rats were treated with progesterone during the 2 days after ovariectomy, the responsiveness of the anterior lobe to dopamine was similar to that in ovariectomized controls. It is suggested that the decrease in the responsiveness of the anterior pituitary gland to the actions of dopamine on lysosomal enzyme activity and PRL release that occurs between diestrus and estrus is estrogen mediated. It is also suggested that the ability of estrogen to antagonize the inhibitory effect of dopamine on PRL release may be mediated through an estrogen-induced reduction in the capacity of dopamine to stimulate lysosomal enzyme activity in the anterior pituitary gland.

Animals↗