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PubMed2000

Neural connections of the anterior hypothalamus and agonistic behavior in golden hamsters.

In male golden hamsters, offensive aggression is regulated by an interaction between arginine-vasopressin and serotonin at the level of the anterior hypothalamus. The present studies were conducted to study a neural network underlying this interaction. The connections of the anterior hypothalamus were examined by retrograde and anterograde tracing in adult male hamsters. Several limbic areas were found to contain both types of tracing suggesting reciprocal connections with the anterior hypothalamus. Their functional significance relating to the consummation of aggression was tested by comparing neuronal activity (examined through quantification of c-Fos-immunolabeling) in two groups of animals. Experimental animals were sacrificed after attacking an intruder. Control animals were sacrificed after exposure to a woodblock carrying the odor of an intruder that elicited behaviors related to offensive aggression without its consummation. An increased density of Fos-immunoreactivity was found in experimental animals within the medial amygdaloid nucleus, ventrolateral hypothalamus, bed nucleus of the stria terminalis and dorsolateral part of the midbrain central gray. These data suggest that these areas are integrated in a neural network centered on the anterior hypothalamus and involved in the consummation of offensive aggression. Finally, c-Fos-immunoreactivity was combined with labeling of serotonin and vasopressin neurons to identify sub-populations particularly associated with offensive aggression. Vasopressin neurons in the nucleus circularis and medial division of the supraoptic nucleus showed increased neuronal activity in the fighters, supporting their role in the control of offensive aggression.

Aggression↗
PubMed2003

Expression of D1 and D2 dopamine receptors in the hypothalamus and pituitary during the turkey reproductive cycle: colocalization with vasoactive intestinal peptide.

The regulation of avian prolactin (PRL) secretion and PRL gene expression is influenced by hypothalamic vasoactive intestinal peptide (VIP), the PRL-releasing factor in avian species. Recent evidence indicates that D(1) and D(2) dopamine (DA) receptors play a pivotal role in VIP and PRL secretion. The differential expression of DA receptors located on hypothalamic VIP neurons and anterior pituitary cells may affect the degree of prolactinemia observed during the turkey reproductive cycle. The relative expression of D(1D) and D(2) DA receptor subtype mRNA was quantitated using in situ hybridization histochemistry (ISH). D(1D) and D(2) DA receptor mRNA was found expressed throughout the hypothalamus and pituitary. The expression of D(1D) DA receptor mRNA in the hypothalamus was found to be 6.8-fold greater than that of D(2) DA receptor mRNA. Higher D(1D) DA receptor mRNA content was found in the anterior hypothalamus (3.6-fold), the ventromedial nucleus (2.0-fold), the infundibular nuclear complex (INF; 1.9-fold), and the medial preoptic nucleus (1.5-fold) of laying hens as compared to that of reproductively quiescent non-photostimulated hens. The levels seen in incubating hyperprolactinemic hens were essentially the same as in laying hens, except for the INF where levels were 52% higher. During the photorefractory stage (hypoprolactinemia), the D(1D) DA receptor mRNA was at its lowest level in all areas tested. No differences were observed in hypothalamic D(2) DA receptor mRNA abundance throughout the reproductive cycle, except for an increase in D(2) DA receptor mRNA within the INF of photorefractory hens. Also, a marked reduction in D(2) DA receptor mRNA was observed in the pituitary of incubating hens. Pituitary D(1D) DA receptor levels did not change when birds entered the incubating phase. Double ISH revealed that D(1D) and D(2) DA receptor mRNAs were co-expressed within neurons expressing VIP mRNA, predominantly within the lateral hypothalamus and INF. D(1D) DA receptor mRNA was more highly expressed than D(2) DA receptor mRNA. The present findings clearly demonstrate that the expression of stimulatory D(1) DA receptor mRNA in the hypothalamus increases in hyperprolactinemic incubating hens, whereas inhibitory D(2) DA receptor mRNA increases in the pituitary of hypoprolactinemic photorefractory hens.

Animals↗
PubMed2006

Exercise enhances insulin and leptin signaling in the cerebral cortex and hypothalamus during dexamethasone-induced stress in diabetic rats.

Exercise and dexamethasone (DEX) are known to have opposite effects on peripheral insulin resistance. However, their effects and mechanism on brain glucose metabolism have been poorly defined. We investigated the modulation of the hypothalamo-pituitary-adrenal (HPA) axis and insulin/leptin signaling associated with glucose utilization in the brains of 90% pancreatectomized diabetic rats, which had been administered two dosages of DEX and exercised for 8 weeks. The data revealed that the administration of a high dose (0.1 mg/kg body weight/day) of DEX (HDEX) attenuated insulin signaling in the cerebral cortex and hypothalamus, whereas exercise potentiated their insulin signaling along with induction of IRS2 expression. In parallel with the modulated signaling, glucose utilization, such as glycogen storage and glycogen synthase activity, was suppressed by DEX in the cortex and hypothalamus, while exercise offset the DEX effects. Despite a decrease in epididymal fat mass, HDEX increased serum leptin levels, possibly due to an activated HPA axis, while exercise suppressed the increment. However, DEX reduced leptin-induced STAT3 phosphorylation in the cortex and hypothalamus, and it increased AMP-activated protein kinase (AMPK) phosphorylation only in the hypothalamus. Exercise reversed the phosphorylation of STAT3 and AMPK which had been modulated by DEX. In conclusion, exercise improves insulin and leptin signaling in the cerebral cortex and hypothalamus of diabetic rats exacerbated with HDEX, contributing to the regulation of body weight and glucose homeostasis.

AMP-Activated Protein Kinase Kinases↗
PubMed1992

Norepinephrine utilization in the hypothalamus of the male rat during adolescent development.

This study examined the influence of adolescent development and pubertal changes in gonadal function on the development of norepinephrine (NE) turnover in the hypothalamus and cerebral cortex of rats from late juvenile to young adult ages. In one study, NE utilization was estimated in intact male rats and in male rats castrated at 14 days of age. NE levels were measured 15, 30, 45, 60, 120, and 240 min after inhibition of catecholamine synthesis at 28, 42, and 70 days of age. In a second study, male rats were made precocious by chronic testosterone exposure over days 14-28 and on the 28th day NE utilization was measured in both the hypothalamus and cerebral cortex. Turnover rates were calculated based on steady-state kinetics. The results indicate that in vivo NE levels and turnover rates in both the hypothalamus and cortex significantly increase from a late juvenile age to adulthood. However, when NE levels measured after synthesis inhibition were expressed as a percentage of the mean basal values, there was a significant effect of age only in the hypothalamus. Hence, the age-related increases in hypothalamic NE turnover appear to reflect age-related changes in NE utilization, whereas the increases in cortical turnover rates reflect the increasing basal levels and not age-related changes in NE utilization. During mid-puberty (42 days), NE utilization in the hypothalamus was markedly different from that observed in this region at either 28 or 70 days. At 28 and 70 days, NE levels decreased to 50% of basal levels by 4 h following synthesis inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Origin of immunoreactive ACTH in brain sites outside the ventral hypothalamus.

Immunoreactive adrenocorticotropin (IR-ACTH) is widely distributed throughout the brain. Highest concentrations have been localized in the ventral hypothalamus, a recognized site of origin of IR-ACTH containing neuronal cell bodies. To determine whether IR-ACTH arises in other brain sites, we determined the effect on the concentration of IR-ACTH in several regions of rat brain after intracerebroventricular injection of colchicine, an agent that inhibits axoplasmic transport and leads to an accumulation of neuronal secretory products within cell bodies. Three regions (ventral hypothalamus, dorsal hypothalamus, amygdala) showed a significant increase in concentration of IR-ACTH after colchicine, whereas the hippocampus and preoptic area did not. Because neuropeptides, in general, undergo posttranslational processing during axoplasmic transport, it could be predicted that inhibition of transport would lead to a relative increase in 'large', precursor forms of hormone in regions containing cells of origin of neuropeptide tracts. Therefore, the effect of colchicine on the processing of molecular forms of IR-ACTH was also examined. In brain regions showing a significant increase in IR-ACTH after colchicine, the proportion of 'big' ACTH and ACTH1-39 (relative to total IR-ACTH) increased and the proportion of 'small' ACTH (less than 4,500 daltons) declined. In contrast, size distribution of IR-ACTH species in other areas were either the opposite or were unchanged. These studies indicate that in addition to the ventral hypothalamus, IR-ACTH also originates in the dorsal hypothalamus and the amygdala, and that decreased axoplasmic peptide transport is associated with decreased processing of molecular forms.

Adrenocorticotropic Hormone↗
PubMed1993

Steroid hormone effects on NMDA receptor binding and NMDA receptor mRNA levels in the hypothalamus and cerebral cortex of the adult rat.

Previous work has demonstrated that N-methyl-D-aspartate (NMDA) is capable of stimulating luteinizing hormone release in a variety of species. Interestingly, the ability of NMDA to stimulate luteinizing hormone release is significantly compromised in castrated male and female rats as compared to intact animals. The purpose of the present study was to determine if a difference exists in the number or affinity of NMDA receptors in the hypothalamus of intact or castrated adult male and female rats and whether steroid replacement has any effect on NMDA receptor binding. NMDA receptor mRNA levels were also determined in the respective models. The cerebral cortex was used as a control to check for specificity of any observed differences. The number of NMDA binding sites in the hypothalamus was found to be approximately 25% of that found in the cerebral cortex and the equilibrium association constant was similar in both tissues. In the female rat, neither ovariectomy nor ovariectomy with estrogen pellet replacement or estrogen and progesterone injections altered NMDA receptor binding or the equilibrium association constant in the hypothalamus or cerebral cortex as compared to intact controls. Similar to the case in the female, NMDA receptor binding in the hypothalamus and cerebral cortex of male rats did not change after castration or after treatment with testosterone propionate. Neither ovariectomy nor ovariectomy with estradiol replacement brought about any change in the NMDA receptor mRNA levels in the hypothalamus. However, in the cerebral cortex ovariectomy with estrogen replacement brought about a small but significant increase in NMDA receptor mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1990

Cholinergic mechanisms in the rat's hypothalamus mediate the stimulatory effect of thyrotropin-releasing hormone on gastric secretion.

To assess the possible involvement of cholinergic mechanisms in the hypothalamic nuclei in the stimulatory effect of TRH on gastric secretion, rats were infused with thyrotropin-releasing hormone (TRH), cholinergic agonist or antagonist, and normal saline through previously implanted hypothalamic cannulae. Administration of TRH or pilocarpine into the lateral cerebral ventricle or the anterior hypothalamus caused a dose-related increase in gastric volume and acidity in rats. On the other hand, administration of either atropine or D-tubocurarine into the same brain sites caused the opposite effects. Furthermore, the stimulatory effect of TRH or pilocarpine on gastric secretion was completely abolished by pretreatment of the CSF or the anterior hypothalamus with atropine and to a lower degree, D-tubocurarine. Administration of TRH, pilocarpine, atropine or D-tubocurarine into the lateral hypothalamus produced only a slight effect on gastric volume and acidity. However, the gastric volume or acidity was not affected by administration of either TRH, pilocarpine, atropine or D-tubocurarine into the ventromedial hypothalamus in our rats. The data indicate that the cholinergic muscarinic receptor mechanisms in the anterior hypothalamus may mediate the stimulatory effect of TRH on gastric secretion in rats.

Animals↗
PubMed2005

Neurosteroids and female reproduction: estrogen increases 3beta-HSD mRNA and activity in rat hypothalamus.

A central event in mammalian reproduction is the LH surge that induces ovulation and corpus luteum formation. Typically, the LH surge is initiated in ovariectomized rats by sequential treatment with estrogen and progesterone (PROG). The traditional explanation for this paradigm is that estrogen induces PROG receptors (PR) that are activated by exogenous PROG. Recent evidence suggests that whereas exogenous estrogen is necessary, exogenous PROG is not. In ovariectomized-adrenalectomized rats, estrogen treatment increases hypothalamic PROG levels before an LH surge. This estrogen-induced LH surge was blocked by an inhibitor of 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (3beta-HSD), the proximal enzyme for PROG synthesis. These data indicate that estrogen induces de novo synthesis of PROG from cholesterol in the hypothalamus, which initiates the LH surge. The mechanism(s) by which estrogen up-regulates neuro-PROG is unknown. We investigated whether estrogen increases 1) mRNA levels for several proteins involved in PROG synthesis and/or 2) activity of 3beta-HSD in the hypothalamus. In ovariectomized-adrenalectomized rats, estrogen treatment increased 3beta-HSD mRNA in the hypothalamus, as measured by relative quantitative RT-PCR. The mRNAs for other proteins involved in steroid synthesis (sterol carrier protein 2, steroidogenic acute regulatory protein, and P450 side chain cleavage) were detectable in hypothalamus but not affected by estrogen. In a biochemical assay, estrogen treatment also increased 3beta-HSD activity. These data support the hypothesis that PROG is a neurosteroid, produced locally in the hypothalamus from cholesterol, which functions in the estrogen positive-feedback mechanism driving the LH surge.

Animals↗
PubMed2006

Phosphoinositide-specific inositol polyphosphate 5-phosphatase IV inhibits inositide trisphosphate accumulation in hypothalamus and regulates food intake and body weight.

The enzyme phosphatidylinositol 3-kinase (PI3-kinase) exerts an important role in the transduction of the anorexigenic and thermogenic signals delivered by insulin and leptin to first-order neurons of the arcuate nucleus in the hypothalamus. The termination of the intracellular signals generated by the activation of PI3-kinase depends on the coordinated activity of specific inositol phosphatases. Here we show that phosphoinositide-specific inositol polyphosphate 5-phosphatase IV (5ptase IV) is highly expressed in neurons of the arcuate and lateral nuclei of the hypothalamus. Upon intracerebroventricular (ICV) treatment with insulin, 5ptase IV undergoes a time-dependent tyrosine phosphorylation, which follows the same patterns of canonical insulin signaling through the insulin receptor, insulin receptor substrate-2, and PI3-kinase. To evaluate the participation of 5ptase IV in insulin action in hypothalamus, we used a phosphorthioate-modified antisense oligonucleotide specific for this enzyme. The treatment of rats with this oligonucleotide for 4 d reduced the hypothalamic expression of 5ptase IV by approximately 80%. This was accompanied by an approximately 70% reduction of insulin-induced tyrosine phosphorylation of 5ptase IV and an increase in basal accumulation of phosphorylated inositols in the hypothalamus. Finally, inhibition of hypothalamic 5ptase IV expression by the antisense approach resulted in reduced daily food intake and body weight loss. Thus, 5ptase IV is a powerful regulator of signaling through PI3-kinase in hypothalamus and may become an interesting target for therapeutics of obesity and related disorders.

Amino Acid Sequence↗
PubMed1982

Immunohistochemical localization of thyrotropin-releasing hormone in the rat hypothalamus and pituitary.

The distribution of immunoreactive TRH in the rat hypothalamus and pituitary was demonstrated using the peroxidase-antiperoxidase technique after rapid fixation of the rat brain with 5% acrolein. Widespread reaction product was identified in neuronal processes throughout the hypothalamus, with dense labeling in the median eminence, dorsomedial nucleus, parvocellular division of the paraventricular nucleus, perifornical region, periventricular nucleus, and organum vasculosum of the lamina terminalis. A striking accumulation of immunoreactive TRH was also noted throughout the posterior pituitary, where fibers appeared to terminate in grape-like swellings. Peroxidase-positive perikarya were best seen after colchicine pretreatment and were distributed in many regions of the hypothalamus. The greatest density of immunoreactive neurons was in the suprachiasmatic preoptic nucleus, parvocellular subdivision of the paraventricular nucleus, perifornical region, dorsomedial nucleus, and baso-lateral hypothalamus. These data are consistent with the role of TRH as a hypophysiotropic hormone, a regulator of the posterior pituitary, and a neurotransmitter or neuromodulator of neurons in other regions of the hypothalamus.

Animals↗
PubMed1983

Changes in somatostatin-like activity in discrete areas of the rat hypothalamus during different stages of proestrus and diestrus and their relation to serum gonadotropin, prolactin, and growth hormone levels.

To investigate physiological changes in the somatotropin release-inhibiting factor (SRIF) content of the hypothalamus during the estrous cycle, groups of 8-10 rats were decapitated every 2 h from 0800-1800 h on proestrus and diestrus. SRIF was assayed in the preoptic suprachiasmatic area, posterior hypothalamus, arcuate nucleus area, and median eminence. Gonadotropins, PRL, and GH were measured in trunk blood and correlated with concentrations of SRIF. A marked decrease in SRIF occurred between 0800-1400 h of proestrus in the preoptic suprachiasmatic area (1.00 +/- 0.28 vs. 0.09 +/- 0.03 micrograms/g wet wt, P less than 0.001) and the posterior hypothalamus (0.43 +/- 0.10 vs. 0.02 +/- 0.004 micrograms/g, P less than 0.001). A similar pattern of decrease in SRIF also occurred in the tissue containing the arcuate nucleus (2.09 +/- 0.37 vs. 0.98 +/- 0.13 micrograms/g, P less than 0.01). In the median eminence the lowest SRIF concentration was measured at 1600 h (31.4 +/- 3.4 vs. 22.0 +/- 1.32 micrograms/g, P less than 0.02). Diestrous values for SRIF did not change in the posterior hypothalamus and arcuate area; however, values increased slightly in the median eminence and decreased in the preoptic suprachiasmatic area between 1400-1800 h. Spearman's correlation coefficient (rs) between PRL and SRIF in the preoptic suprachiasmatic area and the posterior hypothalamus was rs = -0.66 and rs = -0.55 (P less than 0.001), respectively.

Animals↗
PubMed1983

Effect of prostaglandin E1 on vasoactive intestinal polypeptide release from the hypothalamus and on prolactin secretion from the pituitary in rats.

In order to elucidate the mechanisms by which prostaglandin (PG) affects PRL secretion, the effect of PGE1 on vasoactive intestinal polypeptide (VIP) release from the rat hypothalamus was examined by determining plasma VIP levels in rat hypophysial portal blood in vivo and VIP release from the perifused hypothalamus in vitro. Intraventricular injection of PGE1 (1 and 5 micrograms/rat) caused a 2- to 3-fold increase in the concentration of plasma VIP in hypophysial portal blood in anesthetized rats. The flow rate of portal blood was slightly increased after the injection of PGE1. VIP release from the perifused rat hypothalamus was stimulated by high potassium levels (56 mM). The infusion of PGE1 (10 microM) resulted in a significant increase in VIP release from the hypothalamus in vitro. Both these responses were calcium dependent. The intraventricular injection of PGE1 (1 and 5 micrograms/rat) resulted in a dose-related increase in peripheral plasma PRL levels in the rat. These findings suggest that PGE1 plays a stimulatory role in regulating VIP release from the hypothalamus into hypophysial portal blood and causes PRL secretion from the pituitary in rats.

Alprostadil↗
PubMed1990

Glucagon and related peptides in fetal rat hypothalamus in vivo and in vitro.

Proglucagon-derived peptides are localized in pancreas, intestine, and the nervous system. We have examined the ontogeny of glucagon and related peptides in developing rat hypothalamus and have developed a fetal rat hypothalamic cell culture model to study the synthesis and secretion of these peptides in cells of neural origin. Fetal rat hypothalamus (19-21 day gestation) was found to contain glucagon-like immunoreactive (GLI) peptides including glucagon. The relative amounts of two of the GLI peptides (glicentin and oxyntomodulin) increased with development such that adult hypothalamus contained a predominance of these peptides over glucagon. The ratio of GLI peptides to glucagon increased from 2.6 +/- 0.5 in fetus to 46 +/- 11 in adult (P less than 0.001). When fetal rat hypothalamic cells (FRHC) were placed into primary culture for 7 days, the presence of neurons, glial cells, and glucagon-containing cells was detected by immunohistochemical staining. Analysis of proglucagon gene expression in FRHC cultures by Northern blotting demonstrated the presence of a single proglucagon messenger RNA (mRNA) transcript identical in size and sequence to that detected in fetal pancreas and intestine. RNase protection analysis of RNA from FRHC cultures, brainstem, and intestine confirmed that the proglucagon mRNA transcripts present in these three tissues were identical. Analysis of FRHC content of GLI peptides and immunoreactive glucagon demonstrated that peptide levels were not significantly different from those of whole fetal rat hypothalamus, and did not vary significantly throughout 2 weeks in culture. FRHC cultures were found to contain substantial amounts of glucagon after 1 week of culture. Release of the GLI peptides on day 7 of culture was increased 3-fold (P less than 0.001) by treatment of FRHC for 1 h with 5 mM (Bu)2cAMP. Rat hypothalamus therefore appears to undergo unique changes in posttranslational processing of proglucagon during development. Primary cultures of FRHC thus provide a promising in vitro model to study the molecular control of proglucagon biosynthesis and GLI peptide secretion in the brain.

Animals↗
PubMed1991

Angiotensin II increases the corticotropin-releasing factor messenger ribonucleic acid level in the rat hypothalamus.

Angiotensin II (AII) has an important role in the regulation of CRF release. In the present study, the effect of centrally administered AII on CRF messenger RNA (mRNA) levels in the rat hypothalamus was examined. Administration of 0.1 nmol and 1 nmol AII into the lateral ventricle increased the levels of plasma ACTH 20 min and 45 min after administration and those of proopiomelanocortin mRNA in the anterior pituitary (AP) and CRF mRNA in the hypothalamus 2 h after administration. On the other hand, ACTH levels in AP and CRF levels in the median eminence temporarily decreased 45 min after the administration of 1 nmol AII, but it returned to the control level at 90 min. Administration of 10 nmol saralacin, an AII antagonist, blocked 1 nmol AII-induced increase in the levels of plasma ACTH, proopiomelanocortin mRNA in AP, and CRF mRNA in the hypothalamus. These results indicate that central administration of AII increases the CRF mRNA level in the hypothalamus in a receptor-specific manner and also increases CRF release. Therefore, AII seems to have an important role in the regulation of the release and synthesis of CRF in the hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1992

Immunocytochemical localization of progestin receptors in monkey hypothalamus: effect of estrogen and progestin.

The increase in PRL secretion which follows progesterone (P) administration to estradiol (E)-primed women and monkeys cannot be due to an action of P at the pituitary level because lactotropes do not contain progestin receptors (PR). To further the hypothesis that P increases PRL secretion by an action in the hypothalamus, PR-expressing neurons were studied in free-ranging and steroid-manipulated monkeys using immunocytochemistry with a monoclonal antibody to human PR. Specific PR immunoreactivity is localized in the nucleus of individual hypothalamic neurons. Male and female adult and juvenile macaque hypothalami contain significant populations of PR-positive neurons throughout the anterior and medial basal hypothalamus. Ovariectomy decreases, but does not abolish, the number of neurons expressing PR. PR expression was not altered in the supraoptic nucleus (SON) by ovariectomy. Estrogen treatment for 28 days caused a significant increase in the number of PR-positive neurons in the medial preoptic area, the ventro-medial nucleus, the arcuate nucleus, and the median eminence, but not in the SON. P treatment added to the E treatment from day 14 to day 28 did not alter the number of PR-positive neurons in any area. These data suggest that PR may be constitutively expressed in the magnocellular neurons of the SON and in certain other cells throughout the hypothalamus. E induces PR in a large proportion of neurons in the medial basal hypothalamus and this action is not blocked by subsequent P treatment. The inability of P to down-regulate PR in the hypothalamus differs from the reproductive tract and pituitary. Indeed, this observation is consistent with the fact that PRL secretion remains elevated during chronic P administration.

Aging↗
PubMed1993

Estrogen uncouples beta-adrenergic receptor from the stimulatory guanine nucleotide-binding protein in female rat hypothalamus.

The responsiveness of adenylyl cyclase to beta-adrenergic receptor stimulation was investigated in membranes prepared from hypothalamus-preoptic area and cortex of ovariectomized female rats injected with oil vehicle or estradiol benzoate 24 or 48 h before death. Membranes from the hypothalamus-preoptic area of ovariectomized animals displayed a concentration-dependent stimulation of adenylyl cyclase when incubated with the beta-adrenergic receptor agonist, isoproterenol (10(-7)-10(-5) M). This response was suppressed in membranes from estrogen-treated animals. The effect of estrogen was observed 48 h, but not 24 h, after hormone administration. In addition, estrogen had no measurable effect on hypothalamic adenylyl cyclase activation by either GTP (10(-8)-10(-5) M) or forskolin (10(-8)-10(-6) M), on beta-adrenergic receptor density, or on antagonist binding affinity measured with the beta-adrenergic antagonist [125I]iodocyanopindolol. Analysis of isoproterenol displacement of iodocyanopindolol binding revealed that estrogen reduced agonist binding affinity in hypothalamus-preoptic area membranes. In membranes from ovariectomized controls, high affinity agonist binding to the beta-adrenergic receptor was apparent and was abolished by guanine nucleotides. However, membranes from estradiol-treated rats demonstrated only low affinity agonist binding that was unaffected by guanine nucleotides. Estradiol did not detectably alter concentrations of either cholera or pertussis toxin substrates in hypothalamus-preoptic area membranes. These data indicate that estrogen promotes a stable time-dependent desensitization of beta-adrenergic receptor activation of adenylyl cyclase in hypothalamus and preoptic area by uncoupling the receptor from the guanine nucleotide-binding protein, G8.

Adenylyl Cyclases↗
PubMed1998

Differential expression of progestin receptor isoforms in the hypothalamus, pituitary, and endometrium of rhesus macaques.

The progestin receptor exists in at least two isoforms: a long form (PR-B) and a short form (PR-A), which can be separated and detected with Western blot analysis. It has been suggested from in vitro transfection experiments that differential expression of the two isoforms may provide one mechanism for tissue specific actions of progesterone (P). However, more information from in vivo experimentation is needed. It has been reported that P down-regulates the expression of PR in the endometrium and pituitary of E primed macaques. However, PR protein and PR messenger RNA expression in the hypothalamus is maintained with P treatment of E-primed macaques. Thus, there is tissue-specific regulation of PR by its cognate ligand in the nonhuman primate. To gain insight into the tissue-specific regulation of PR by P, we questioned whether differential expression of the isoforms of PR exists in the endometrium, pituitary, and hypothalamus of rhesus monkeys. The expression of PR-A and PR-B was examined after E (28-30 days) and E + P (14 days E + 14 days E + P) treatment in the primate endometrium, pituitary, and hypothalamus. After E or E + P treatment, the levels of PR-A were 5 times higher than PR-B in the endometrium. PR-A was 1.6-fold higher than PR-B in the pituitary. In the hypothalamus, the ratio of A to B ranged from less than 1 (B exceeds A) to unity (A and B equimolar). There was no difference in the ratio of A to B between E-treated and E + P-treated groups in any tissue examined. These observations (a) provide further support of the hypothesis that differential expression of the isoforms of PR may subserve the tissue specific actions of P and (b) also suggest that P does not differentially affect the expression of the isoforms of its cognate receptor in the endometrium, pituitary, or hypothalamus.

Animals↗
PubMed2005

Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus.

CONTEXT: Recent findings point to an increasing number of hypothalamic proteins involved in the central regulation of thyroid hormone feedback. The functional neuroanatomy of these proteins in the human hypothalamus is largely unknown at present. OBJECTIVE: The aim of this study was to report the distribution of type II and type III deiodinase (D2 and D3) as well as the recently identified T(3) transporter, monocarboxylate transporter 8 (MCT8), in the human hypothalamus. DESIGN: The study included enzyme activity assays, immunocytochemical studies, and mRNA in situ hybridizations in postmortem human hypothalamus (n = 9). RESULTS: D2 immunoreactivity is prominent in glial cells of the infundibular nucleus/median eminence, blood vessels, and cells lining the third ventricle. By contrast, both D3 and MCT8 are expressed by neurons of the paraventricular (PVN), supraoptic, and infundibular nucleus (IFN). In support of these immunocytochemical data, D2 and D3 enzyme activities are detectable in the mediobasal human hypothalamus. Combined D2, D3, MCT8, and thyroid hormone receptor immunohistochemistry and TRH mRNA in situ hybridization clearly showed that D3, MCT8, and thyroid hormone receptor isoforms are all expressed in TRH neurons of the PVN, whereas D2 is not. CONCLUSIONS AND IMPLICATIONS: Based on these findings, we propose three possible routes for thyroid hormone feedback on TRH neurons in the human PVN: 1) local thyroid hormone uptake from the vascular compartment within the PVN, 2) thyroid hormone uptake from the cerebrospinal fluid in the third ventricle followed by transport to TRH neurons in the PVN or IFN neurons projecting to TRH neurons in the PVN, and 3) thyroid hormone sensing in the IFN of the mediobasal hypothalamus by neurons projecting to TRH neurons in the PVN.

Adult↗