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PubMed1990

Changes in glucocorticoid receptor number in the hypothalamus and pituitary of the sheep fetus with gestational age and after adrenocorticotropin treatment.

The concentrations of ACTH and cortisol both rise in the plasma of fetal lambs during late pregnancy, reflecting maturation of the fetal hypothalamic-pituitary-adrenal axis and providing the stimulus for parturition. The failure of rising cortisol to suppress plasma ACTH may be due to altered sensitivity of glucocorticoid negative feedback. To examine the possibility that this effect might be mediated through changes in the number of glucocorticoid receptors (GR) in the fetal hypothalamus and pituitary, we measured changes in GR number in these tissues from fetuses at discrete times of pregnancy between day 60 and term (day 145) and from newborn lambs and adult sheep. We also determined the effect of intrafetal ACTH administration in amounts known to produce premature parturition on GR number in fetuses at days 125-130 of gestation. Binding of [1,2,4-N-3H]triamcinolone acetonide to dispersed cell preparations of fetal pituitary and hypothalamus was saturable, temperature dependent, glucocorticoid specific, and of high affinity (2-3 X 10(-9) M). The number of GR in the pituitary always exceeded that in the hypothalamus. In both tissues GR number rose between days 60-70 to highest values on days 100-110, then decreased until day 125. GR number in the pituitary rose again at term, paradoxically at a time of rising endogenous glucocorticoid levels. However, after ACTH administration, there was a significant decrease in GR number in both hypothalamus and pituitary. These results indicate that altered efficacy of glucocorticoid negative feedback in term fetuses is not due to a decrease in pituitary or hypothalamic GR number. The rise in GR number at term and the fall after intrafetal ACTH treatment raises the possibility that mechanisms exist in the fetus allowing normal autoregulation of GR to be overridden at term.

Adrenocorticotropic Hormone↗
PubMed1990

Divergent effects of insulin on insulin-like growth factor-II gene expression in the rat hypothalamus.

The effect of peripheral insulin treatment on brain content and synthesis of insulin-like growth factor-II (IGF-II) was studied in acute and chronic conditions. After a 3-h hyperinsulinemic/euglycemic clamp, rats were killed, and brains were removed for IGF-II analysis. Insulin infusion elevated IGF-II concentrations in the dorsomedial hypothalamus (DMH) and suprachiasmatic nucleus, but decreased IGF-II in the paraventricular nucleus, lateral hypothalamus (LtH), and supraoptic nucleus compared to values in control animals. In separate parallel studies, the effects of 4 days of insulin injection (1 U insulin/rat, sc, twice daily) on brain IGF-II mRNA and peptide were determined. For RNA analysis the hypothalamus was divided into three regions (lateral, ventral, and dorsal). IGF-II mRNA content was shown to vary by an order of magnitude within the adult rat hypothalamus under control conditions, and there appeared to be a differential region-dependent response to insulin treatment. Relative abundance of IGF-II mRNA in control hypothalami was VH much greater than cortex greater than or equal to LtH greater than DMH. IGF-II mRNA content declined after insulin treatment in the VH, but rose in all other regions. Insulin increased IGF-II peptide content in the paraventricular nucleus, LtH, and VMH but decreased IGF-II in the DMH and suprachiasmatic nucleus. These results indicate that peripheral insulin status may be an important factor in the synthesis and secretion of IGF-II in the brain.

Animals↗
PubMed1990

Release of substance P from rat hypothalamus and pituitary by endothelin.

Endothelin-1 is a 21 amino acid peptide originally isolated from porcine aortic endothelium and has recently been localized within the central nervous system. We have administered endothelin-1 in a dynamic perfusion system in order to study its possible effects on the rat hypothalamus and anterior pituitary. Tissue (hypothalami or quartered pituitaries) was placed into plastic chambers and was perfused with oxygenated Krebs-bicarbonate solution. After an interval to establish stable basal peptide release, endothelin-1 was administered at two doses (0.1 and 1 microM) and the release of substance P, vasoactive intestinal peptide, 7B2, and somatostatin was measured, the last being detectable only in hypothalamic perfusates. Both concentrations of endothelin-1 led to a significant increase (P less than 0.01) in the release of substance P from the hypothalamus and pituitary, but not of vasoactive intestinal peptide, 7B2, or somatostatin. Thus after the 0.1 microM and 1 microM endothelin-1 perfusion substance P release from the hypothalamus increased by 125 +/- 5% and 215 +/- 15% (mean +/- SEM) of basal and from the pituitary by 168 +/- 8% and 276 +/- 15% (mean +/- SEM). No change occurred in the output of ACTH or other pituitary hormones. The release of substance P from hypothalamus or pituitary after stimulation with endothelin-1 was not blocked when a calcium free medium was used. Endothelin-1 binding sites were identified on rat pituitary cell membranes. These findings suggest the possibility that endothelin may act as a paracrine substance, neurotransmitter, or neuromodulator in the hypothalamo-pituitary axis.

Animals↗
PubMed1976

The channeling of natural stimuli that evoke the ejection of milk in the rat. Effect of transections in the midbrain and hypothalamus.

The afferent and the efferent pathways of the milk ejection reflex were studied in conscious lactating rats subjected to suckling after experiencing stereotaxically-controlled transections in the midbrain or hypothalamus. Extensive transections in midbrain or hypothalamus. Extensive transections in the midbrain or caudal hypothalamus blocked reflex milk ejection while less extensive cuts, sparing either the dorsal or the ventral fibers, did not. The frontal plane immediately caudal to the neurosecretory nuclei intersects both afferent and efferent fibers. All cuts at this plane, regardless of size, caused blockage whenever the neurosecretory fibers located at the lateral ventral hypothalamus were severed. A multiple cut in the near vicinity of both supraoptic nuclei caused blockage of milk ejection, probably by severing the combined neurosecretory tract originating in both the supraoptic and paraventricular nuclei. If the multiple cut was performed unilaterally, a blockage of milk ejection was not observed, indicating that reflex action can be sustained by preserving one side of the neurosecretory pathway. Simple cuts in the same region revealed that the efferent pathway takes on a caudo-medial direction towards the neurohypophysis. In the near vicinity of the infundibulum, simple cuts showed that the efferent fibers enter the infundibulum from the sides, and also established that the milk ejection reflex persisted even when a small number of fibers in the pituitary stalk remained intact. The results showed that the afferent pathway for the reflex is diffuse, while the efferent pathway is compact. Only complete transection of one of the two pathways caused blockage.

Afferent Pathways↗
PubMed1976

Dopamine/neuroleptic receptors in basal hypothalamus and pituitary.

In order to determine whether the basal hypothalamus or the pituitary (or both) is the likely locus of action of the tuberoinfundibular (TI) dopamine neurons, these regions were examined for dopamine and neuroleptic receptors. High affinity receptors for haloperidol and dopamine were found in the rat pituitary while none were detected in rat basal hypothalamus. The relative ability of two neuroleptics, chlorpromazine and haloperidol, to displace (3H)haloperidol from the receptor in monkey pituitary is similar to that for rat striatum. The lack of receptors capable of binding (3H)haloperidol or (3H)dopamine in the basal hypothalamus strongly suggests that the TI neurons do not produce postsynaptic effects in this region. The pituitary receptors for (3H)haloperidol and (3H)dopamine have the characteristics of a functional system. The presence of neuroleptic/dopamine receptors in the pituitary and lack of such receptors in the basal hypothalamus supports the hypothesis that dopamine may act directly as a prolactin release inhibiting factor (PIF) rather than releasing PIF from adjacent nerve terminals in the median eminence.

Animals↗
PubMed1992

Detection of prolactin receptor (PRL-R) mRNA in the rat hypothalamus and pituitary gland.

Prolactin receptor (PRL-R) mRNAs exist in several tissues where prolactin is known to act including the liver, testes, prostate, ovary, mammary gland, adrenal gland and kidney. PRL also acts at the level of the hypothalamus and pituitary gland to feed back and regulate its own secretion and the secretion of other anterior pituitary hormones. Therefore, we hypothesized that PRL-R mRNA would exist in these target tissues as well. Total RNA was extracted from rat anterior and medial basal hypothalamus, anterior and posterior pituitary gland, cerebral cortex, skeletal muscle and liver. After reverse transcribing total RNA with Murine-MLV reverse transcriptase and random or oligo(dT) pmers, the polymerase chain reaction (PCR) was performed. PCR products were then analyzed by ethidium bromide staining. Using primers that flanked the coding region for the extracellular binding domain we detected PRL-R mRNA in the anterior and medial basal hypothalamus, anterior and posterior pituitary gland, as well as in the liver, but not in the cerebral cortex or skeletal muscle. In addition, when we used primers that distinguish the long and short forms of the PRL-R mRNA, both forms of the PRL-R mRNA were detectable in the same tissues. Our data suggest that PRL may feed back at the level of the hypothalamus and pituitary gland through the same short and/or long PRL-R mRNA that mediate PRL action in the peripheral tissues.

Animals↗
PubMed1992

Evidence of a corticotropin-releasing hormone pulse generator in the macaque hypothalamus.

The secretion of hormones from the hypothalamic-pituitary axis is, in general, characterized by an episodic pattern of release. In the adrenal axis, ACTH and cortisol levels in peripheral blood display irregularly pulsatile ultradian patterns that are superimposed on the well characterized circadian rhythm. While it is generally accepted that CRH is released from the hypothalamus in a similar manner, very few studies have actually examined the temporal release of CRH. To examine the temporal release of CRH directly, we have established an in vitro perifusion system using the hemisectioned macaque hypothalamus. Perifusate samples were collected at 10-min intervals for 20 h and assayed for CRH by RIA. In control animals, a very regular, pulsatile pattern of hormone release was present, with a pulse interval of 90 +/- 11 min. Although this interval closely approximates the average pulse interval of ACTH and cortisol in the human, the regular pattern revealed in our study has not been demonstrated previously in the adrenal axis in vivo and suggests that factors outside the hypothalamus play a major role in controlling adrenal hormone levels. When hypothalami were perifused with dexamethasone added to the culture medium, no change in pulsatile activity was detected, indicating that a site outside of the hypothalamus may function as the primary center of feedback inhibition by adrenal glucocorticoids in the central nervous system. Because the very regular pulses of CRH that we observed bear striking similarity to the circhoral pulses of GnRH, we speculate that CRH may play a more subordinate role in regulating the adrenal axis and that other releasing factors and/or feedback effects at the pituitary level may be more important in the generation of the irregularly pulsatile, circadian patterns of ACTH and cortisol seen in peripheral blood.

Animals↗
PubMed1992

Neuropeptide-Y innervation of beta-endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis.

Central administration of neuropeptide-Y (NPY) inhibits pituitary LH release in ovariectomized rats and stimulates LH release in intact and ovariectomized rats pretreated with ovarian steroids. Although the precise neural mechanism of this dual effect of NPY is not known, experimental evidence suggests an underlying interaction between hypothalamic NPY and the inhibitory beta-endorphin (beta END) systems in the neuroendocrine regulation of pituitary LH release in the rat. The present study was undertaken to examine the morphological basis of the interaction between these two peptidergic systems in the hypothalamus. Sections of the mediobasal hypothalamus of colchicine-pretreated female rats were double immunostained for NPY and beta END and examined by light and electron microscopy. The light brown diaminobenzidine reaction was used to visualize beta END cells, while NPY neurons were labeled with a dark blue nickel ammonium sulfate-intensified diaminobenzidine reaction. Under the light microscope, a dense network of NPY-immunoreactive axons and axon terminals was observed in close apposition with beta END-immunoreactive neurons throughout the medial basal hypothalamus. Electron microscopic examination revealed that NPY-immunoreactive boutons formed axosomatic and axo-dendritic synaptic connections with beta END cells. A majority of these synaptic membrane specializations appeared asymmetrical [corrected]. In light of the previous evidence of excitatory and inhibitory effects on LH release and the existence of direct synaptic connections between NPY and LHRH neurons in the hypothalamus, the current results imply that the dual effects of NPY on LH secretion may involve modulation of LHRH secretion, both by the direct route and indirectly through the hypothalamic beta END system.

3,3'-Diaminobenzidine↗
PubMed1993

Intraventricular administration of histidyl-proline-diketopiperazine [Cyclo(His-Pro)] suppresses prolactin secretion and synthesis: a possible role of Cyclo(His-Pro) as dopamine uptake blocker in rat hypothalamus.

Histidyl-proline-diketopiperazine [Cyclo (His-Pro) (CHP)] was discovered to be one of the metabolites of TRH. To understand the specific role of CHP in rat hypothalamic dopamine neurons, we examined the in vivo effects of intraventricular (icv) infusion of CHP on the release and synthesis of PRL in the rat pituitary and the 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine ratio in the rat hypothalamus. We also examined the in vitro effects of CHP on the release of [3H]dopamine from dispersed tuberoinfundibular dopamine neurons, [3H]dopamine reuptake in hypothalamic membrane fractions, and PRL release from rat pituitary cultured cells. Female rats were treated by icv infusion of 1 microM CHP daily for 1, 3, and 7 days, using Alzet osmotic pumps. After 1 day of treatment, the serum PRL concentration was significantly decreased. Northern blot analysis of the total RNA isolated from the pituitary glands of control animals using 32P-labeled PRL cDNA as a probe indicated the presence of PRL gene transcript, 1.0 kilobase in size, and its amount was decreased by CHP treatment. CHP did not affect [3H]dopamine release from dispersed tuberoinfundibular dopaminergic neurons at any concentration up to 1 microM. CHP did not inhibit PRL release from cultured pituitary cells at low concentrations (1-100 nM), but it stimulated PRL release at high concentrations (1 and 10 microM). We also examined the concentrations of dopamine and DOPAC in the rat hypothalamus when CHP was administered icv for 1 or 7 days. There was a significant decrease in the DOPAC/dopamine ratio after CHP treatment for 1 day. Furthermore, CHP caused dose-dependent inhibition of [3H]dopamine uptake by the rat hypothalamus similar to other dopamine uptake blockers, such as benztropine and GBR12909. These data suggest that icv administration of CHP might decrease both PRL secretion and accumulation of PRL gene transcripts in the pituitary by decreasing the DOPAC/dopamine ratio and inhibiting dopamine reuptake in the rat hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Differential regulation of epidermal growth factor and transforming growth factor-alpha messenger ribonucleic acid in the rat anterior pituitary and hypothalamus induced by stresses.

Evidence has shown that epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are present in the anterior pituitary as well as the hypothalamus, and that EGF can influence the function of pituitary cells, particularly corticotropes in vivo and in vitro. However, little is known about their exact functional roles and how they are regulated in these two areas. The present study was designed to determine if EGF and TGF alpha messenger RNA (mRNA) are expressed in the rat anterior pituitary and hypothalamus and how stress conditions such as cold, ether, or restraint affect their local expression. A sensitive mRNA detection method, the ribonuclease protection assay, detected both EGF and TGF alpha mRNA in the rat anterior pituitary and hypothalamus. Reverse transcription-polymerase chain reaction (RT-PCR) further showed the presence of EGF and TGF alpha mRNA in these two areas and several other rat tissues (submandibular gland, liver, kidney, lung cerebral cortex, and testis). No TGF alpha mRNA was found in the kidney, however. EGF mRNA was up-regulated in the anterior pituitary after 30 min acute cold stress (CS) and restrainer-restraint stress (RS) but not 30 min after ether stress (2 min, ES), novelty stress (NS), or tape-restraint stress (TS). Further analysis showed that EGF mRNA expression decreased after 1 h CS (1C) and then increased after 3 h CS (3C). In contrast, TGF alpha mRNA in the anterior pituitary and hypothalamus and hypothalamic EGF mRNA did not show significant changes in response to either acute stresses (CS, ES, RS, TS, NS) or longer CS (1C, 3C). Our results suggest that 1) EGF, is up-regulated after some stresses; 2) increased pituitary EGF mRNA in response to stresses varies with the type of stress; and 3) pituitary TGF alpha and hypothalamic EGF and TGF alpha may be not involved in the stress response.

Adrenocorticotropic Hormone↗
PubMed1997

Leptin activates neurons in ventrobasal hypothalamus and brainstem.

Leptin is a circulating protein secreted by adipocytes which has profound feeding, metabolic, and neuroendocrine effects. Leptin receptors have been localized to the hypothalamus, but the anatomic sites responsible for mediating the effects of circulating leptin have not been demonstrated. We report that systemic administration of leptin activates nuclear groups in the ventrobasal hypothalamus, including the ventromedial, dorsomedial, and ventral premammillary hypothalamic nuclei. Leptin also activated the parvicellular subdivisions of the paraventricular hypothalamic nucleus that project to parasympathetic and sympathetic preganglionic neurons. Finally, leptin administration activated the superior lateral parabrachial subnucleus, a nuclear group containing cholecystokinin neurons that project to the ventrobasal hypothalamus. These findings indicate that circulating leptin activates specific nuclear groups in the hypothalamus and brainstem known to regulate complex physiological responses during times of substrate availability.

Animals↗
PubMed1998

The generation of nitric oxide and carbon monoxide produces opposite effects on the release of immunoreactive interleukin-1beta from the rat hypothalamus in vitro: evidence for the involvement of different signaling pathways.

Both the cytokine, interleukin-1 (IL-1), and the gaseous neurotransmitters, nitric oxide (NO) and carbon monoxide (CO), have been implicated in the control of neuroendocrine functions, such as the release of CRH and luteotropic hormone-releasing hormone from the hypothalamus. Though increased levels of IL-1 in this brain region are unambiguously associated with enhanced CRH and reduced luteotropic hormone-releasing hormone release, the net effects of the two gases are still unclear, but in vivo and in vitro evidence suggests that the generation of NO and CO within the hypothalamus might counteract the stimulatory effects of IL-1 and bacterial lipopolysaccharide on the neuroendocrine stress axis. In this study, we have investigated the effects of NO and CO on the release of immunoreactive (ir)-IL-1beta from the rat hypothalamus in vitro. It was observed that the NO donor, sodium nitroprusside (SNP), stimulates ir-IL-1beta release under basal conditions, whereas the increase in CO levels obtained with hemin, the CO precursor through the heme oxygenase pathway, has no effect on basal ir-IL-1beta release but inhibits release stimulated by high K+ concentrations. The opposite effects of the two gases on cytokine release seemed to be caused by the activation of different signaling pathways, because: 1) SNP, but not CO-saturated solutions, is able to increase cyclic GMP levels in hypothalamic tissue; 2) CO-saturated solutions increase PGE2 production and release from the hypothalamic explants, whereas SNP has no effect; 3) SNP-stimulated ir-IL-1beta release is counteracted by a selective inhibitor of soluble guanylyl cyclase, LY 83583, but not by a cyclooxygenase inhibitor, indomethacin; and 4) conversely, indomethacin, but not LY 83583, reverses the inhibitory effect of hemin on K+-stimulated ir-IL-1beta release. It is concluded that NO and CO signal in the rat hypothalamus via the activation of soluble guanylyl cyclase and cyclooxygenase, respectively.

Animals↗
PubMed1999

The human growth hormone-releasing hormone transgenic mouse as a model of modest obesity: differential changes in leptin receptor (OBR) gene expression in the anterior pituitary and hypothalamus after fasting and OBR localization in somatotrophs.

We reported previously an increase in leptin receptor (OBR) gene expression in the anterior pituitary of human GH-releasing hormone (hGHRH) transgenic mice. The primary goal of this study was to investigate the possible mechanisms regulating OBR expression in these mice. Compared with normal sibling controls, hGHRH transgenic mice had significantly greater amounts of abdominal fat, higher levels of leptin messenger RNA (mRNA), and a 2-fold increase in plasma leptin concentrations. Despite normal plasma glucose levels, hGHRH transgenic mice had 4.5-fold elevated levels of plasma insulin. Using a ribonuclease protection assay, we measured the mRNA levels of the OBR long form (OBR(L)) in the anterior pituitary and hypothalamus after 48 h of fasting. In the anterior pituitary, food deprivation induced dramatic increases in OBR(L) mRNA levels in both normal and transgenic mice. In contrast, in the hypothalamus, fasting resulted in a significant decrease in OBR(L) gene expression in normal mice, and no changes were detected in hGHRH transgenic mice. Using dual in situ hybridization, OBR(L) mRNA was detected in somatotrophs. Moreover, the number of OBR(L)-positive pituitary cells as well as the percentage of OBR(L)-positive cells that express GH mRNA were increased in transgenic mice. In conclusion, 1) the modest obesity in hGHRH transgenic mice is associated with increases in leptin synthesis and secretion as well as insulin secretion; 2) GH and/or GHRH as well as leptin and insulin may differentially contribute to the changes in OBR(L) gene expression in the anterior pituitary and the hypothalamus; 3) the response of OBR(L) gene expression in the hypothalamus to fasting is absent in the modestly obese hGHRH transgenic mice; and 4) somatotrophs are target cells for leptin, and the increase in OBR(L) gene expression in the pituitary of hGHRH transgenic mice is due at least in part to the increase in the number of cells expressing OBR(L).

Adipose Tissue↗
PubMed2000

Differential regulation of leptin transport by the choroid plexus and blood-brain barrier and high affinity transport systems for entry into hypothalamus and across the blood-cerebrospinal fluid barrier.

Leptin is a circulating hormone that controls food intake and energy homeostasis. Little is known about leptin entry into the central nervous system (CNS). The blood-cerebrospinal fluid (CSF) barrier at the choroid plexus and the blood-brain barrier (BBB) at the cerebral endothelium are two major controlling sites for entry of circulating proteins into the brain. In the present study, we characterized leptin transport across the blood-CSF barrier and the BBB by using a brain perfusion model in lean rats. Rapid, high-affinity transport systems mediated leptin uptake by the hypothalamus (KM = 0.2 ng/ml) and across the blood-CSF barrier (KM = 1.1 ng/ml). High affinity in vivo binding of leptin was also detected in the choroid plexus (KD = 2.6 ng/ml). In contrast, low affinity carriers for leptin (KM = 88 to 345 ng/ml) were found at the BBB in the CNS regions outside the hypothalamus (e.g. cerebral cortex, caudate nucleus, hippocampus). Our findings suggest a key role of high affinity leptin transporters in the hypothalamus and choroid plexus in regulating leptin entry into the CNS and CSF under physiological conditions. Low affinity transporters at the BBB outside the hypothalamus could potentially contribute to overall neuropharmacological effects of exogenous leptin.

Animals↗
PubMed2002

Genistein affects ER beta- but not ER alpha-dependent gene expression in the hypothalamus.

Isoflavone phytoestrogens are growing increasingly popular because of their reported cardiovascular and anticarcinogenic properties, but the effects of these compounds in the brain are largely unknown. In a previous study, we found that an isoflavone supplement, containing a mixture of soy phytoestrogens, inhibited estrogen-dependent female sexual behavior and was antiestrogenic for both ER alpha- and ER beta-dependent gene expression in the hypothalamus. Here we examined the impact of the soy isoflavone genistein, a major component of the supplement, on estrogen-dependent female sexual behavior and ER alpha- and ER beta-dependent gene expression in the rat brain. Genistein, at a dietary concentration of 100 or 500 ppm had no effect on lordosis behavior in rats. However, at 500 ppm genistein had differential activity through ER alpha and ER beta in the hypothalamus. Genistein had no effect, in either the presence or absence of 17 beta-E2, on oxytocin receptor density in the ventromedial nucleus of the hypothalamus, an estrogen-dependent action thought to be regulated via ER alpha. However, genistein increased ER beta mRNA expression in the paraventricular nucleus of the hypothalamus by 24%, whereas 17 beta-E2 decreased ER beta mRNA expression by 26%, a process likely mediated by ER beta itself. These results suggest that at this dose, genistein has antiestrogenic action through ER beta in the paraventricular nucleus but negligible activity through ER alpha in the brain.

Animals↗
PubMed1996

Gonadotropin-releasing hormone gene expression is increased in the medial basal hypothalamus of postmenopausal women.

Quantitative In situ hybridization and computer-assisted microscopy were used to compare GnRH gene expression in the hypothalamus of premenopausal and postmenopausal women. Hypothalamic sections were incubated with 35S-labeled 48-base complementary DNA probes and dipped into nuclear emulsion for visualization of messenger ribonucleic acids at the single cell level. Two subtypes of GnRH neurons were examined: heavily labeled GnRH neurons located primarily in the medial basal hypothalamus (type I) and lightly labeled neurons in the dorsal preoptic-septal region (type II). We report a 50% increase in mean number of silver grains per type I neuron in the medial basal hypothalamus of postmenopausal women. In contrast to type I neurons, there was no difference in the number of grains per type II neuron in the dorsal preoptic-septal regions. The mean profile area and the number of type I GnRH neurons per section were not different between the two groups, and there was no change in the size of type II neurons. There was also a significant postmortem degradation of messenger ribonucleic acid in type I, but not type II, neurons. We hypothesize that the increase in GnRH gene expression in the medial basal hypothalamus of postmenopausal women is secondary to the ovarian failure of menopause and is not a nonspecific effect of age. The differential response of the two types of hypothalamic neurons provides additional evidence that distinct functional subgroups of GnRH neurons exist in the human brain.

Adult↗
PubMed1988

Glucocorticoid regulation of proopiomelanocortin messenger ribonucleic acid content of rat hypothalamus.

We have verified the possibility that the POMC gene of the rat hypothalamus might be subject to regulation by glucocorticoids. Adrenalectomy increased the concentration of POMC mRNA in anterior pituitary and in hypothalamus, but not in the neurointermediate lobe of the pituitary gland. Dexamethasone and, to a slightly lesser extent, corticosterone treatments reversed the adrenalectomy-induced increase in POMC mRNA concentrations in both anterior pituitary and hypothalamus. Dexamethasone caused a slight decrease of POMC mRNA levels in the neurointermediate lobe of the pituitary gland, while corticosterone had no effect. These results indicate that the POMC gene of the rat brain hypothalamus is also under negative control by glucocorticoids.

Adrenalectomy↗
PubMed1990

Isolation and characterization of the human gonadotropin-releasing hormone gene in the hypothalamus and placenta.

The GnRH gene has been cloned in several species, but the location of the promoter and the exact start of transcription have not previously been determined. To characterize the low abundance human GnRH mRNA in the hypothalamus and placenta, we have employed the polymerase chain reaction. The hypothalamus was found to have a 61-base pair first exon, and its transcriptional start site was determined. The human hypothalamic GnRH cDNAs isolated thus far have all contained a short 5' untranslated region which would correspond to this start site. However, all human placental GnRH cDNAs reported to date have a long 5' untranslated region, which extends more than 140-base pairs 5' to this start site in the hypothalamus, suggesting the utilization of an alternative promoter in the placenta. In addition, the human GnRH gene undergoes differential splicing in these tissues. The first intron is removed from the hypothalamic, but retained in the placental, GnRH mRNA. Thus, the placenta has a very long first exon, while the hypothalamus has a comparatively short first exon, followed by a long first intron. This characterization of the human GnRH gene will now allow hormonal regulatory studies to be performed using gene transfer techniques.

Base Sequence↗