Biomedical subjects

W W Vale

Publications and source records attributed to W W Vale.

At least 127 records · Page 7Linked to original sources

PubMed1989

Circulating inhibin alpha concentrations in infant, prepubertal, and adult male rhesus monkeys (Macaca mulatta) and in juvenile males during premature initiation of puberty with pulsatile gonadotropin-releasing hormone treatment.

Circulating inhibin alpha concentrations were determined in infant, juvenile, and adult male rhesus monkeys with a RIA employing antisera to a synthetic fragment of the alpha-subunit of porcine inhibin. Binding of tracer, [DSer1,Nle5]human inhibin alpha(1-25)-Gly-125I-Tyr, to antibody was inhibited by standard, [DSer1,Nle5]human inhibin alpha(1-25)-Gly-Tyr. and by plasma from adult male monkeys in a parallel fashion. Castration in adults resulted in a 5-fold decline in the levels of immunoreactivity in plasma. Mean (+/- SE) plasma inhibin alpha concentrations in infants and adults (322.9 +/- 51.9 and 460.1 +/- 43.9 pg/ml, respectively) were significantly higher (P less than 0.05) than those in juveniles (191.3 +/- 28.3 pg/ml). Moreover, initiation of puberty in juvenile males, 13-18 months of age, with a chronic (10- to 12-week) intermittent iv infusion of GnRH (0.1 microgram/min for 3 min every 3 h) resulted in a progressive rise in circulating inhibin alpha that plateaued, after 5 weeks of pituitary stimulation, at concentrations (343.9 +/- 38.2 pg/ml) comparable to those of infants and adults and twice those observed before initiation of the pulsatile infusion of GnRH. Circulating FSH concentrations increased during the first week of GnRH stimulation from 2.7 +/- 0.1 ng/ml before treatment to 6.0 +/- 1.2 ng/ml, where they remained for the duration of the experiment. Testosterone secretion during the initiation of precocious puberty occurred in discrete episodes that were robustly correlated with GnRH-induced LH discharges. In contrast, changes in circulating inhibin alpha concentrations over the 3-h interval between GnRH pulses were unremarkable. Activation of Sertoli and Leydig cells during initiation of puberty in the juvenile males, as reflected by circulating inhibin alpha and testosterone concentrations, respectively, occurred with similar time courses. At the time of orchidectomy, 10-12 weeks after initiation of GnRH treatment, testicular tissue was prepared for histological examination. In spite of a 2-fold gain in testicular weight and in hypertrophy of Sertoli cells in association with GnRH stimulation, maturation of the germinal epithelium did not progress past prophase I spermatocytes, and the number of these latter cells was meager. These findings indicate that the testis of the infant primate, like that of the adult, secretes significant amounts of inhibin, and that the quiescent Sertoli cell of the juvenile males may be readily provoked by appropriate gonadotropin stimulation into producing inhibin. The results also fail to provide evidence for the view that changes in circulating inhibin concentrations are robustly related, in an inve

Aging↗

PubMed1989

Gonadotropin and alpha-subunit responses to chronic gonadotropin-releasing hormone analog administration in patients with glycoprotein hormone-secreting pituitary tumors.

Pituitary tumors secreting intact glycoprotein hormones (LH, FSH, and TSH) and/or alpha-subunit are being increasingly recognized. Because chronic administration of GnRH analogs decreases gonadotropin secretion in normal subjects, we investigated gonadotropin and alpha-subunit responses to chronic GnRH analog administration in five men with glycoprotein hormone-secreting pituitary tumors. Two patients (patients A and B) received the GnRH agonist analog (D-Trp6-Pro9-NEt-LHRH) for 4 weeks as a daily sc dose (8 micrograms/kg.day). In both, secretion of LH and/or alpha-subunit increased markedly. Subsequently, three patients received a higher analog dose (32 micrograms/kg.day) for a longer duration (8 weeks). One patient with a LH- and FSH-secreting tumor (patient C) had a highly significant (P less than 0.001) fall in serum LH and FSH concentrations; however, alpha-subunit secretion increased. During a subsequent study, when this patient received a lower dose (8 micrograms/kg.day) for 8 weeks, gonadotropin suppression also occurred. In two additional patients who received this dose (32 micrograms/kg.day), it had a persistent agonist effect on FSH beta (patient D) and alpha-subunit secretion (patient E). A marked increase in alpha-subunit secretion occurred in all five patients, regardless of whether basal serum alpha-subunit concentrations were elevated. These patients received the GnRH analog at doses 2-8 times greater than those that suppress gonadotropin secretion in normal men. Serum LH and FSH concentrations decreased in only one patient with a gonadotropin-secreting adenoma. The serum LH and FSH responses to acute GnRH stimulation did not predict the gonadotropin responses to chronic GnRH analog administration. Thus, gonadotropin and alpha-subunit production by most pituitary adenomas is augmented during chronic GnRH analog administration, consistent with defective GnRH desensitization in the adenomatous tissue. Despite the heterogeneous gonadotropin responses to the GnRH analog in these patients, serum alpha-subunit levels increased in all patients, indicating dissociation in the secretion of intact gonadotropins and alpha-subunit.

Adenoma↗

PubMed1989

Mode of suppression of pituitary and gonadal function after acute or prolonged administration of a luteinizing hormone-releasing hormone antagonist in normal men.

LHRH antagonists compete with endogenous LHRH for binding to receptors on pituitary gonadotrophs and thereby inhibit gonadotropin secretion and, consequently, gonadal function. We studied the pituitary and gonadal suppression following single doses and short term administration (1-3 weeks) of a recently developed LHRH antagonist in normal men. First, the antagonist Nal-Glu ([Ac-D2Nal1, D4ClPhe2,D3Pal3,Arg5,DGlu6(AA),DAla10]LHRH ), was given as a single sc injection to five normal men at three dose levels of 1, 5, and 20 mg (study I). Serum FSH, immunoreactive LH (IR-LH), bioactive LH (bio-LH), testosterone, and estradiol were measured before and at frequent intervals for 48 h after Nal-Glu administration. Mean serum FSH decreased (P less than 0.001) by 28.9 +/- 5.4% (+/- SE), 38.2 +/- 7.9%, and 44.5 +/- 3.6% after the 1-, 5-, and 20-mg doses, respectively. Mean serum IR-LH decreased (P less than 0.001) by 39.0 +/- 13.8%, 53.2 +/- 10.0%, and 53.1 +/- 14.4% after the three doses. Serum bio-LH levels and the ratio of bio-LH/IR-LH decreased (P less than 0.001) after the 20-mg dose by 87.8% and 78.5%, respectively. Serum testosterone levels decreased (P less than 0.001) more than 78.5% after all Nal-Glu doses. The duration of testosterone suppression, but not the nadir reached, was dose dependent (P = 0.012). Serum estradiol levels also decreased (P less than 0.001), but the rate of decrease was slower than that of serum testosterone. The apparent plasma disappearance half-life of Nal-Glu after administration of 5 mg was 12.8 +/- 2.7 h. The Nal-Glu antagonist also was given daily as a single sc injection of 5 mg to eight normal men for 21 days (study II) or twice daily to five men for 7 days (study III). In study II, serum FSH, IR-LH, bio-LH, testosterone, estradiol, and 17-hydroxy-progesterone were measured daily, immediately before the next injection, and on days 1, 7, and 21 in frequent blood samples drawn for 24 h. The mean serum testosterone level in study II decreased (P less than 0.001) from 17.6 +/- 2.2 to 4.1 +/- 1.0 nmol/L on day 1, increased (P less than 0.05) between days 2 and 8, and then progressively decreased to below 2 nmol/L from day 18 until 24 h after the end of the study. Serum FSH, IR-LH, and bio-LH levels paralleled those of testosterone.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1989

The importance of luteinizing hormone in the control of inhibin and progesterone secretion by the human corpus luteum.

Serum inhibin levels rise markedly during the luteal phase of the human menstrual cycle and are closely correlated with serum progesterone (P) levels, suggesting that the corpus luteum (CL) secretes inhibin. While FSH is the major regulator of inhibin secretion by the granulosa cells, the control of CL inhibin secretion is unclear. We hypothesized that, like P, CL inhibin secretion would be LH dependent. To examine this possibility, normal women were given the GnRH antagonist [Ac-D2Nal1, D4CL Phe2, D3Pal3, Arg5, DGlu6 (AA), DAla10]GnRH (Nal-Glu antagonist) for 3 consecutive days commencing on day 6-8 of the luteal phase. The daily doses were 2.5 (n = 3), 10 (n = 4), and 25 micrograms/kg (n = 5), sc. Serum LH levels fell 2 h after injection, and the fall was maximal (70-74%) at 6 h; the degree of suppression was not dose dependent. The duration of suppression was dose related, being less than 12 h, between 12, and 24 h, and more than 24 h for the 2.5, 10, and 25 micrograms/kg doses, respectively. Serum FSH levels declined by 22-43%, but the effect was not dose related. Serum P levels fell by 42-45% 8 h after each dose of antagonist. They returned to baseline 24 h after the 2.5 micrograms/kg dose, but after both the 10 and 25 micrograms/kg doses serum P levels continued to fall, and menstrual bleeding commenced within 48-72 h after the first antagonist injection. Serum inhibin levels were not altered relative to normal cycles by the 2.5 micrograms/kg dose, but fell by 48% and 58%, and 62% and 73% respectively, 48 and 72 h after the 10 and 25 micrograms/kg doses, respectively. Serum P and inhibin levels correlated closely in all women. To examine the relative roles of FSH and LH in the control of CL function, Nal-Glu antagonist (25 micrograms/kg, sc) was administered at 0 and 24 h commencing on day 6-8 of the luteal phase, in combination with either human menopausal gonadotropin (hMG; 150 IU, im, every 12 h) or hCG (1500 IU, im, once), both commencing at 0 h. hMG administration led to a rapid (by 2 h) and marked (3- to 9-fold) rise in serum FSH levels, whereas serum LH remained low, similar to antagonist alone treatment cycless.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1989

A comparison of the suppressive effects of testosterone and a potent new gonadotropin-releasing hormone antagonist on gonadotropin and inhibin levels in normal men.

GnRH antagonists have been developed in large part because of their potential use as contraceptive agents, particularly in men. Specifically, it was hoped that GnRH antagonists combined with testosterone (T) would be a more effective contraceptive regimen than T alone. We compared the suppressive effects of a potent GnRH antagonist, Na1-Glu [AcD2NaL1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA),+ ++DAla10-GnRH], and of T together and separately on serum and urinary gonadotropin and serum inhibin levels in normal men. Ten-day courses of Nal-Glu (75 micrograms/kg; Nal-Glu alone), 200 mg testosterone enanthate, im, on days 0 and 7 (T alone), and the combination (Na1-Glu + T) were given to nine men. Serum gonadotropin and inhibin concentrations decreased after 1-2 days of Na1-Glu administration, while gonadotropin suppression occurred more slowly after T alone. Serum T fell to 30% of baseline values during Na1-Glu administration. The combination of Na1-Glu + T was more effective in suppressing serum LH, FSH, and inhibin than was either Na1-Glu alone or T alone. All hormone levels returned to baseline levels within 2.5 weeks after the end of the three regimens. We conclude that the Na1-Glu GnRH antagonist effectively inhibits gonadotropin, inhibin, and sex steroid secretion when given daily for 10 days and that the administration of Nal-Glu + T results in more complete gonadotropin and gonadal suppression than that produced by either agent given alone. These results encourage further investigation of the combination of a GnRH antagonist and T as a male contraceptive regimen and of the antagonist alone as a treatment for hormone-dependent neoplasia.

Adult↗

PubMed1988

Glucocorticoid toxicity in the hippocampus: in vitro demonstration.

Glucocorticoids (GCs) disrupt the energy metabolism of neurons of the hippocampus, and thus leave them more vulnerable to a variety of damaging metabolic insults. In this manner, GCs appear to influence the rate of hippocampal neuron loss during aging in the rat, as well as the severity of hippocampal damage following hypoxia-ischemia or seizure. These GC actions could be secondary to their multitudinous peripheral actions. The present report, however, suggests that GCs directly endanger hippocampal neurons. Glucocorticoid-induced sensitization of neurons to damaging toxins was demonstrated in vitro. The viability of primary cultures of dispersed fetal rat hippocampal neurons was assessed following exposure to a variety of neurotoxins. Prior incubation of the cultures with the rodent-typical GC, corticosterone, significantly decreased neuronal viability in the face of the toxins. Such compounds included the glutaminergic excitotoxin kainic acid, the antimetabolite 3-acetylpyridine and the superoxide radical generator paraquat. As little as 10(-9) M corticosterone could potentiate damage, a concentration equivalent to low basal values in vivo. Higher concentrations of corticosterone could potentiate damage even further; these corticosterone concentrations were not themselves damaging. Administration of glucose increased neuronal viability in the face of the GC/toxin combination, without increasing viability following toxin alone. This suggests that a critical feature of the action of GCs on neurons might be the inhibition of glucose utilization (which is a hallmark of peripheral GC action).

Animals↗

PubMed1988

Acromegaly from ectopic growth hormone-releasing hormone secretion by a malignant carcinoid tumor. Successful treatment with long-acting somatostatin analogue SMS 201-995.

A 26-year-old man with acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) secretion by a metastatic carcinoid tumor is the subject of this study. He previously failed to respond to conventional therapeutic modalities (partial hypophysectomy, pituitary irradiation, high-dose bromocriptine and a combination of streptozotocin and 5-fluorouracil) and was treated with long-acting somatostatin analogue SMS 201-995 (Sandoz, East Hanover, NJ). Growth hormone and somatomedin C concentrations became normal, and GHRH-LI (GHRH-like immunoreactivity) was suppressed by more than 60%. The growth hormone response to exogenous GHRH 1-40 was stopped and growth hormone rise to thyrotropin-releasing hormone (TRH) was significantly attenuated. A significant shrinkage of the pituitary gland was observed. Similarly, the size of the metastatic carcinoid lesions decreased dramatically and was accompanied by a normalization of liver function. After almost 2 years of SMS 201-995 therapy, the patient was well and had no clinical signs of acromegaly. Thus, SMS 201-995 appears to be a remarkably effective agent for treatment of acromegaly secondary to ectopic GHRH secretion.

Acromegaly↗

PubMed1988

Effects of [D-Arg6, Trp7, Leu8, Pro9NEt]-luteinizing hormone-releasing hormone (sGnRH-A) and [D-Ala6, Pro9NEt]-luteinizing hormone-releasing hormone (LHRH-A), in combination with pimozide or domperidone, on gonadotropin release and ovulation in the Chinese loach and common carp.

The effects of LHRH-A and sGnRH-A alone and in combination with the dopamine receptor antagonists pimozide (PIM) and domperidone (DOM) on stimulation of gonadotropin (GtH) secretion and ovulation in Chinese loach (Paramisgurnus dabryanus) and common carp (Cyprinus carpio) were studied. When tested in the absence of a dopamine receptor antagonist, sGnRH-A was about 10-fold more potent than LHRH-A in stimulating GtH secretion in loach, whereas these peptides were of similar effectiveness in common carp. Both peptides were effective alone in inducing ovulation in loach, but were ineffective in common carp. PIM and DOM stimulate a small but significant increase in serum GtH, and greatly potentiate the effects of LHRH-A and sGnRH-A on GtH secretion and ovulation in both species. DOM was of equal or somewhat greater potency than PIM in potentiating the action of releasing hormone agonists in loach; however, DOM had markedly greater effectiveness in common carp. sGnRH-A in the presence of DOM was more effective than LHRH-A in stimulating GtH secretion and ovulation in common carp. The present studies suggest that there are marked differences in the relative contribution of GnRH and dopamine in the control of GtH secretion in loach and common carp, and indicate in particular that the more intense dopaminergic inhibitory control of GtH release in common carp modifies the responsiveness of the pituitary to GnRH peptides.

Animals↗

PubMed1988

Growth hormone response to growth hormone-releasing factor in depression.

A blunted growth hormone (GH) response to clonidine and other pharmacologic stimuli has been reported in patients with depression. This blunted growth hormone response to clonidine has led to the speculation that there is a central alpha-2 adrenergic receptor subsensitivity in depression. This hypothesis is based on the assumption that the pituitary somatotroph response to growth hormone-releasing factor (GHRF) is not altered in depression. In the present preliminary study, the somatotroph response to GHRF in depressed patients and normal controls has been evaluated in four depressed patients and four age- and sex-matched controls. The GH response to GRF is highly variable both in normal individuals and in the depressed patients studied. Larger numbers of patients and controls must be studied before any definitive conclusions can be drawn about GH responses to GRF in depressed patients.

Depressive Disorder↗

PubMed1988

Stress-induced gastrointestinal secretory and motor responses in rats are mediated by endogenous corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) has been implicated as a central nervous system mediator of stress. This study examined the effects of CRF and stress on gastric secretory and gastrointestinal motor functions in rats. Partial body restraint as a stress-producing stimulus significantly decreased gastric acid secretion, gastric emptying, and small bowel transit but markedly increased large bowel transit. Corticotropin-releasing factor given cerebroventricularly mimicked the gastrointestinal secretory and motor responses induced by partial body restraint. Cerebroventricular administration of a specific CRF receptor antagonist, alpha-helical CRF-(9-41), but not of the CRF fragment CRF-(1-20), prevented the gastrointestinal secretory and motor responses elicited either by partial body restraint or by exogenous administration of CRF in a dose-dependent fashion. These results suggest that the gastrointestinal secretory and motor responses in rats produced by stress (partial body restraint) are mediated by the endogenous release of CRF. They also indicate that CRF exerts its central nervous system actions on the gastrointestinal tract by a receptor-mediated event.

Animals↗

PubMed1988

Regulation of corticotropin-releasing factor secretion in vitro by glucose.

The neurosecretory responses of the isolated rat hypothalamus were assessed in vitro. Rat hypothalamic blocks were incubated for 30 min in a N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered salt solution with 5.5 mM glucose (base-line collection period). The blocks were transferred to fresh buffer with a new concentration of glucose with or without various additions (test period); corticotropin-releasing factor (CRF) and other hormones in the media were determined by radioimmunoassay. CRF secretion was maximally increased to approximately 200% of base line at glucose concentrations less than 4 mM and decreased to 65% of base line at higher glucose concentrations. The increase in CRF secretion at low glucose (0.55 or 1.38 mM) was Ca2+ dependent and completely reversible. Hexamethonium, cyproheptadine, and atropine partially blocked the CRF response to 0.55 mM glucose. Glucose concentrations from 0 to 11 mM had no effect on the CRF response to 47.5 mM KCl. The inhibitory effects of high glucose were completely reversed by the addition of 2-deoxy-D-glucose (3-49 mM). Glucose levels did not alter secretion of either gonadotropin-releasing hormone or arginine vasopressin from hypothalamic blocks. The results suggest that the isolated rat hypothalamus is extremely sensitive to the level of glucose and that CRF is rapidly and reversibly secreted in response to slight reductions in glucose concentrations. These concentrations are consistent with those observed during moderate to severe hypoglycemia in vivo. The rise in glucocorticoids observed in vivo during hypoglycemia may result at least in part from the ability of the hypothalamus to directly sense glucose levels and promote secretion of CRF.

Animals↗

PubMed1988

Growth hormone-releasing factor stimulation test in depression.

The authors administered the growth hormone-releasing factor (GRF) stimulation test to 19 patients with major depression and 19 age- and sex-matched control subjects to test the hypothesis that a blunted growth hormone (GH) response to clonidine reflects a central alpha 2-adrenergic receptor subsensitivity in depression. GH response to GRF was significantly higher in patients with depression than in control subjects. This group difference was mainly attributable to three of the 19 depressed patients who exhibited markedly high GH responses to GRF. These results suggest that the blunted GH response to clonidine seen in patients with depression is not due to a pituitary defect in GH secretion.

Adult↗

PubMed1988

Inhibin production by primary Sertoli cell-enriched cultures: regulation by follicle-stimulating hormone, androgens, and epidermal growth factor.

Inhibin levels in the serum-free media of primary Sertoli cell-enriched (SCE) cultures were studied as a function of time and hormonal treatment. SCE cultures were established from 20-day-old rats and maintained in SF media supplemented with insulin, transferrin, epidermal growth factor (EGF), and bacitracin. Radioimmunoassayable inhibin was measured using an antibody directed against a synthetic porcine inhibin-alpha (pI alpha) and measured using this same synthetic peptide as well as a highly purified ovine inhibin standard. Results of these determinations are expressed in terms of a synthetic peptide as femtomoles of pI alpha-(1-26)-G-Y-per ml/10(6) cells. Inhibin levels (+/- SEM) that accumulated at this rate in media from control cultures were 184.9 +/- 6.1 and 167.4 +/- 5.2 on days 0-4 and 4-8, respectively. When FSH (oFSH 17; 1-1000 ng/ml) was added, a dose-dependent increase in inhibin levels was significant at all time points beyond the initial 24 h. The simultaneous addition of 2 x 10(-7) M testosterone (T) with low doses of FSH addition of 2 x 10(-7) m testosterone (T) with low doses of FSH suppressed the inhibin response to FSH, but when T was combined with 300 ng/ml FSH, there was no effect of T on inhibin levels compared to FSH alone, regardless of time in culture. In spite of the modest effect of T, androstenedione (A; 2 x 10(-13) to x 10(-5) M) produced a dose-dependent suppression of inhibin levels. This inhibition was also observed at all doses of FSH. The action of A was not due to its conversion to estrogens, as 17 beta-estradiol had no effect on inhibin production by SCE cultures in either the presence or absence of FSH. The effect of EGF, a component of the basal serum-free medium, was next examined; it produced a 1.5-fold higher level of inhibin (188.7 +/- 9.5) compared to cultures without EGF (135.6 +/- 5.0). When SCE cultures were plated with FSH plus EGF, the stimulation of inhibin levels was additive. We conclude that in Sertoli cell cultures established from immature rats (1) the accumulation of inhibin in medium declines from 90 fmol/10(6) cells.day (initial 24 h) to 40-50 fmol/10(6) cells.day (over the first 48 h) and continues to accumulate in the medium for 8 days of culture; (2) FSH regulates the production of inhibin by Sertoli cells; the best dose response is observed over a 3-day period.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗

PubMed1988

Hormonal effects of single gonadotropin-releasing hormone antagonist doses in men.

To assess its gonadotropin-inhibiting potency in man, three different doses of a GnRH antagonist [( Ac-D2-Nal1,D4-Cl-Phe2, D3-Pal3, Arg5,D4-p-methoxybenzoyl-2-amino butyric acid6,D-Ala10]GnRH; Nal-Glu GnRH antagonist) were given to six normal men. Single sc doses of 0.5, 1.5, and 5.0 mg Nal-Glu GnRH decreased mean serum immunoactive LH (iLH) to 45.0 +/- 5.7% (+/- SE), 37.0 +/- 4.9%, and 31.3 +/- 4.2% of baseline, respectively. Maximal suppression occurred between 4 and 8 h after drug injection. Serum bioassayable LH concentrations significantly diminished 8 h after injection of 1.5 and 5.0 mg GnRH antagonist, but not after the 0.5-mg dose. Mean serum testosterone (T) fell to 39.8 +/- 5.0%, 32.1 +/- 4.9%, and 20.7 +/- 4.4% of baseline, respectively, after the 0.5-, 1.5-, and 5.0-mg doses. The decreases in serum iLH and testosterone (T) were more sustained after the higher doses; serum iLH and T were significantly suppressed 24 h after administration of the 5.0-mg dose. Twenty-four-hour integrated serum iLH and T concentrations decreased in a dose-dependent manner. However, basal and 24-h integrated serum FSH concentrations were not significantly affected by the drug. No adverse systemic side-effects occurred. Thus, the Nal-Glu GnRH antagonist effectively decreases serum LH and T concentrations in a dose- and time-dependent manner, and it, therefore, has potential as a male contraceptive.

Adult↗

PubMed1988

Effects of growth hormone-releasing factor and somatostatin on growth hormone secretion in hypophysial stalk-transected beef calves.

The effects of growth hormone-releasing factor (GHRF) on growth hormone (GH) secretion were studied in beef calves after hypophysial stalk transection (HST). Peripheral GH concentration during surgery was elevated for 60 min after the initiation of anesthesia to 15 ng/ml, which was greater than plasma levels after HST and during the recovery period (0-30 hr mean, 3 ng/ml; P less than 0.05). Episodic GH secretion normally seen in sham-operated controls (SOC) was abolished after HST. Before HST, calves responded to 80% of the GHRF challenges, whereas after HST calves responded to every challenge of GHRF with an increase in plasma GH. A dose of 0.067 microgram human pancreatic (hp) hpGHRF(1-40)OH/kg body wt 3 days after HST increased plasma GH to 55 ng/ml from a control period mean of 5 ng/ml (P less than 0.04). On Day 8, HST calves received two injections of 0.067 microgram hpGHRF/kg body wt at 3-hr intervals, with feeding 70 min after the first injection. During two preinjection control periods, basal GH averaged less than 4 ng/ml and increased to 17 (P less than 0.02) and 9 (P less than 0.04) ng/ml immediately after the first and second injection of hpGHRF, but the response declined over the 8-day period after surgery. On Days 19 and 20, the HST calves were infused iv with 0.033 and 0.067 microgram somatostatin(SS)-14 (SRIH)/kg body wt, during which a pulse injection of 0.067 microgram hpGHRF/kg body wt was administered. GH increased to 9 and 5 ng/ml during the 0.033- and 0.067-microgram SRIH infusions after GHRF; no somatotropic rebound was observed after the SRIH was discontinued as was seen in the animals while the hypothalamic-hypophysial connections were intact. Five and six months after HST the responses to two analogs of rat hypothalamic GHRF were similar to those in SOC calves. These results indicate that HST calves responded to exogenous GHRF with an abrupt increase in plasma GH, but GH response to GHRF during SRIH infusion was greatly inhibited.

Animals↗

PubMed1988

Increased potency and sustained suppressive actions of a new gonadotropin-releasing hormone (GnRH) antagonist peptide in man.

We have used a new potent GnRH antagonist to assess the efficacy of suppression of gonadotropin secretion in healthy postmenopausal women at three different doses. The Nal-Glu antagonist produced significant suppression of immunoactive and bioactive LH at a 300 micrograms/kg dose throughout the 30-hr sampling interval with only minimal local (skin) histamine release. This increased potency and decreased skin reactivity of the Nal-Glu antagonist make it a drug with potential clinical use similar to the GnRH agonist, but with the advantage of immediate gonadotropin suppression.

Female↗

PubMed1987

Corticotropin-releasing hormone (CRH) is decreased in the basal ganglia in Huntington's disease.

Corticotropin-releasing hormone-like immunoreactivity (CRH-IR) was measured in control and Huntington's disease brain tissues obtained postmortem. The concentration of CRH-IR was markedly decreased in the caudate/putamen in Huntington's disease; the concentration of somatostatin-like immunoreactivity measured in the same extracts was significantly increased in the caudate/putamen in Huntington's disease compared with the control group. In contrast to previously reported decreases in CRH-IR in the cerebral cortex in Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy, no significant differences were observed in the concentrations of CRH-IR between controls and Huntington's disease in frontal, parietal, temporal, occipital and cingulate cortex and in globus pallidus.

Adult↗

PubMed1987

Beta-endorphin regulation of FSH-stimulated inhibin production is a component of a short loop system in testis.

Inhibin, a hormone produced by Sertoli cells in response to FSH, regulates androgen production in nearby Leydig cells. Beta-endorphin synthesized by Leydig cells under LH control is also known to regulate Sertoli function. To delineate whether beta-endorphin might constitute part of a short loop regulatory system between these two testicular cells, the effect of this opiate on inhibin secretion was examined. Beta-endorphin alone did not alter basal inhibin accumulation in primary Sertoli cell-enriched cultures, however it did significantly reduce FSH-induced inhibin production and adenylyl cyclase activity but had no effect on forskolin-stimulated inhibin accumulation or adenylyl cyclase activity. Other opioid peptides (ACTH, dMSH, methionine-enkephalin) were without effect. These observations suggest that beta-endorphin regulates inhibin secretion by inhibiting FSH receptor coupling to adenylyl cyclase.

Adenylyl Cyclases↗