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G L Jackson

Publications and source records attributed to G L Jackson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of infusing gamma-aminobutyric acid receptor agonists and antagonists into the medial preoptic area and ventromedial hypothalamus on prolactin secretion in male sheep.

We investigated the effects of gamma-aminobutyric acid (GABA) agonists muscimol and baclofen (GABA(A) and GABA(B) agonists, respectively) and antagonists bicuculline methiodide (BMI, GABA(A) antagonist) or 2-hydroxysaclofen (SAC) and CGP 55845A (GABA(B) antagonists) on prolactin (PRL) secretion in castrated rams. The drugs were applied by microdialysis into either the medial preoptic area (mPOA) or ventromedial hypothalamus (VMH). Dialysis of baclofen into the mPOA significantly increased mean PRL (p < 0.05), whereas SAC caused a small, but significant decrease (p < 0.01). Dialysis of either muscimol or BMI into the mPOA had no effect on prolactin. In the VMH, baclofen significantly increased (p < 0.01) mean PRL but SAC and CGP 55845A were ineffective, whereas dialysis of either muscimol or BMI increased mean prolactin (p < 0.01). These results show that infusion into the mPOA of drugs that affect GABA(B) receptor alter PRL release, whereas infusion of a GABA(A) agonists and antagonist was without effect on PRL release. In contrast, infusion of both GABA(A) and GABA(B) agonists and a GABA(A) antagonist into the VMH altered PRL secretion. This suggest that GABAergic neurons in both regions participate in regulating PRL secretion, but by different receptor systems.

Animals↗
PubMed1997

The GnRH system of seasonal breeders: anatomy and plasticity.

Seasonal breeders, such as sheep and hamsters, by virtue of their annual cycles of reproduction, represent valuable models for the study of plasticity in the adult mammalian neuroendocrine brain. A major factor responsible for the occurrence of seasonal reproductive transitions is a striking change in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the inhibitory effects of gonadal steroids. However, the neural circuitry mediating these seasonal changes is still relatively unexplored. In this article, we review recent findings that have begun to define that circuitry and its plasticity in a well-studied seasonal breeder, the ewe. Tract tracing studies and immunocytochemical analyses using Fos and FRAs as markers of activation point to a subset of neuroendocrine GnRH neurons in the MBH as potential mediators of pulsatile GnRH secretion. Because the vast majority of GnRH neurons lack estrogen receptors, seasonal changes in responsiveness to estradiol are most probably conveyed by afferents. Two possible mediators of this influence are dopaminergic cells in the A14/A15 cell groups of the hypothalamus, and estrogen receptor-containing cells in the arcuate nucleus that project to the median eminence. The importance of GnRH afferents in the regulation of season breeding is underscored by observations of seasonal changes in the density of synaptic inputs onto GnRH neurons. Thyroid hormones may participate in this remodeling, because they are important in seasonal reproduction, influence the morphology of other brain systems, and thyroid hormone receptors are expressed within GnRH neurons. Finally, in the hamster, neonatal hypothyroidism affects the number of caudally placed GnRH neurons in the adult brain, suggesting that thyroid hormones may influence development of the GnRH system as well as its reproductive functions in the adult brain.

Animals↗
PubMed1997

Identification and distribution of neuroendocrine gonadotropin-releasing hormone neurons in the ewe.

The final common pathway controlling reproductive function in vertebrates is the GnRH neuron and its projection to the median eminence (ME), site of peptide release into the pituitary portal system. GnRH neurons are widely distributed; therefore we sought to test the hypothesis that those projecting to the ME are located in specific regions. We used as a model the sheep, a species in which a great deal of information regarding the physiology of GnRH secretion is known. To identify cells projecting to the ME (i.e., neuroendocrine neurons), ewes (n = 10) received injections into the ME of neuronal tract-tracing compounds: cholera toxin-beta subunit (CT-beta) or one of two fluorescent compounds (rhodamine isothiocyanate or fluorescein-conjugated dextran). Forty-eight h later, animals were perfused intracranially and their brains were processed for immunocytochemical localization of GnRH and CT-beta using a dual-immunofluorescent procedure or by single-label immunofluorescent visualization of GnRH combined with direct visualization of fluorescent tracers. Small, well-circumscribed injections into the ME were made successfully in 6 of 10 animals, and these overlapped the location of GnRH terminals and fibers. Neuroendocrine GnRH neurons (those GnRH neurons containing retrogradely transported tracer) were identified throughout their previously reported range: within the diagonal band of the Broca/medial septal region, medial preoptic area (MPOA), anterior hypothalamic area, and medial basal hypothalamus. Although the absolute number of neuroendocrine GnRH neurons varied by region, the percentage of the total GnRH population within each of these areas that was retrogradely labeled did not differ (p > 0.05). Injections placed unilaterally within the ME labeled a similar proportion of GnRH cells both ipsilateral and contralateral to the injection site in all areas except the MPOA, where ipsilaterally labeled cells were approximately twice as numerous as those labeled contralaterally. Injections that missed the ME and were placed either into the third ventricle or into the arcuate nucleus labeled only 0.5% and 4-11% of GnRH neurons, respectively. These results do not support the hypothesis that in the ewe, GnRH neurons projecting to the ME are localized to specific regions. Thus, we postulate that GnRH release into the hypophyseal portal system reflects the output of GnRH neurons located in multiple areas.

Animals↗
PubMed1997

Neonatal hypothyroidism permanently alters follicle-stimulating hormone and luteinizing hormone production in the male rat.

Transient neonatal hypothyroidism, induced with the goitrogen 6-n-propyl-2-thiouracil (PTU), results in dramatic increases in both testis size and sperm production in the adult rat. The observed increases in testis size and function occur in the presence of normal circulating testosterone levels. However, circulating gonadotropin levels are chronically reduced by 30-50% at all times in treated males. To better understand the permanent reduction in serum gonadotropin levels following transient neonatal hypothyroidism, we conducted a series of experiments to evaluate pituitary and hypothalamic function in the adult male PTU-treated rat. PTU treatment led to a significant reduction in GnRH-stimulated LH production. Castration resulted in 3.9- to 8.5-fold increases in circulating gonadotropin levels in both treated and control males; however, the absolute increases were significantly reduced in treated males. In contrast to circulating levels, pituitary gonadotropin contents did not increase in treated males after castration. PTU treatment did not lead to a reduction in the density of either luteotropes or folliculotropes, and both cell types increased in size and density after castration. The relative concentrations of both gonadotropin beta-subunit messenger RNAs increased more slowly in treated males than in controls after castration. Thus, although treated rats have the intrinsic ability to produce normal circulating levels of LH and FSH, gonadal feedback and an overall reduction in gonadotrope synthetic ability combine to produce the chronically reduced circulating levels of these hormones.

Animals↗
PubMed1997

Hypothalamic sites of action for testosterone, dihydrotestosterone, and estrogen in the regulation of luteinizing hormone secretion in male sheep.

Testosterone (T) inhibits LH secretion partly by acting at unknown sites within the brain to inhibit GnRH secretion. We tested the hypothesis that the preoptic area (POA) and arcuate-ventromedial region (ARC/VMR), areas rich in androgen and estrogen (E) receptors, are neural sites at which T and the T metabolites, dihydrotestosterone (DHT) and estrogen (E), act to suppress LH secretion. Bilateral guide cannulae were surgically implanted into either the POA or ARC/VMR of castrated male sheep. Experiments were conducted under a long day photoperiod to maximize the inhibitory effect of the steroids. In Exp 1, all sheep (n = 6/site) sequentially received bilateral implants of cholesterol (CHOL), T, or E at each site. Jugular blood samples were taken at 10-min intervals for 4 h both immediately before implant insertion and 5 days later. In Exp 2, all sheep (n = 6/site) sequentially received bilateral implants of CHOL, DHT, or E at each site according to a latin square design. Blood samples were taken before and 7 days after implant insertion. In Exp 3, which followed the same design as Exp 2, implants of E, T, or DHT were placed only in the ARC/VMR. In the final experiment, the effects of T and CHOL implants in the ARC/VMR were compared. Neither T, DHT, nor CHOL implants at either site affected LH secretion. In contrast, E treatment in the ARC/VMR suppressed mean plasma LH levels (P < 0.01), primarily due to an increase in interpulse interval (P < 0.01). Estrogen implants in the POA caused a small, but nonsignificant (P > 0.05), decrease in mean LH levels in the first experiment and an increase in LH interpulse interval (P < 0.05) in the second experiment. These results suggest that the ARC/VMR and possibly the POA are sites at which E acts to reduce GnRH secretion in male sheep.

Animals↗
PubMed1996

Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes.

OBJECTIVE: To determine if suppressive acyclovir therapy given to term gravidas experiencing a first episode of genital herpes simplex virus (HSV)-infection during pregnancy decreases the need for cesarean delivery for that indication. METHODS: Forty-six pregnant women with first episodes of genital herpes during pregnancy were randomly assigned to receive oral acyclovir 400 mg or placebo, three times per day, from 36 weeks' gestation until delivery as part of a prospective, double-blind trial. Herpes simplex virus cultures were obtained when patients presented for delivery. Vaginal delivery was permitted if no clinical recurrence was present; otherwise, a cesarean was performed. Neonatal HSV cultures were obtained and infants were followed-up clinically. RESULTS: None of the 21 patients treated with acyclovir and nine of 25 (36%) treated with placebo had clinical evidence of recurrent genital herpes at delivery (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.002-0.745; P = .002). No woman treated with acyclovir had a cesarean for herpes, compared with nine of 25 (36%) of those treated with placebo (OR 0.04, CI 0.002-0.745; P = .002). No patient in either treatment group experienced asymptomatic genital viral shedding at delivery. No neonate had evidence of herpes infection or adverse effects from acyclovir. CONCLUSION: Suppressive acyclovir therapy reduced the need for cesarean for recurrent herpes in women whose first clinical episode of genital HSV occurred during pregnancy. Suppressive acyclovir treatment did not increase asymptomatic viral shedding and was not harmful to the term fetus.

Acyclovir↗
PubMed1996

Evaluation of suprapubic bladder aspiration for detection of group B streptococcal antigen by latex agglutination in neonatal urine.

Our objective was to determine whether urine collection by suprapubic bladder aspiration (SBA) improves the specificity of the group B streptococcal (GBS) latex agglutination (LA) test by avoiding contamination of urine with GBS from perineal and rectal colonization that can result in a positive LA test in an uninfected infant when the urine is collected by bag. Part 1 consists of a retrospective review of the medical records of 113 infants who had urine collected by SBA for GBS LA testing as part of evaluation for possible sepsis. The sensitivity and specificity of the urine LA test was assessed by comparing it with blood culture results. In part 2, a prospective analysis was performed of 19 newborns who had rectal and vaginal/penile cultures as well as urine by SBA and bag for GBS cultures and LA. Results of LA testing on urine collected by both of these methods were compared with results of urine, perineal, and rectal cultures. In the retrospective review of GBS LA testing performed on 113 consecutive urine specimens collected by SBA from neonates being evaluated for suspected sepsis, the sensitivity and specificity were 67% and 89%, respectively, when compared with blood culture results. Twelve infants who had a positive LA test result but a sterile blood culture (BC-,LA+) were compared with 95 infants with both blood cultures and urine LA tests negative for GBS (BC-, LA-). BC-, LA+ infants were more likely than those with BC-, LA- to have an immature to total neutrophil (I/T) ratio > or = 0.16 at 12 and 24 hours (p = 0.04 and 0.02, respectively). In the prospective study, we found that a positive GBS LA test can be due to perineal contamination and possibly to gastrointestinal absorption of GBS antigen. No false positive LA test results occurred on urine obtained by SBA; however, use of this method failed to detect the one infant with GBS bacteremia. Because of suboptimal sensitivity and specificity, use of the GBS LA test on urine obtained either by SBA or bag cannot be recommended for diagnosis of early onset GBS disease.

Antigens, Bacterial↗
PubMed1996

A subset of estrogen receptor-containing neurons project to the median eminence in the ewe.

The neural pathways responsible for conveying the steroid feedback signals that ultimately affect reproductive neuroendocrine function remain largely undefined. One possibility involves a direct projection from estrogen receptor (ER)-containing neurons to the median eminence (ME), a site of neuroendocrine peptide release. To examine this possibility, 8 ewes received stereotaxic injections of the retrograde neuronal tract-tracing compound cholera toxin-beta subunit (CT beta) into the ME. Neurons sending projections to the ME and containing ER were identified using a dual-label immunoperoxidase method. Double-labeled cells were found in distinct regions: (1) the ER-rich arcuate nucleus (ARC) that contained the greatest number of double-labeled cells, and (2) the organum vasculosum of the lamina terminalis (OVLT) which contained a very consistent, but low, number of double-labeled cells. While a fairly large number of retrogradely-labeled ARC neurons containing ER were identified, the majority of ER-containing ARC neurons were unlabeled and thus send projections elsewhere. Other regions containing high concentrations of ER-positive cells such as the medial preoptic area (MPOA), anterior hypothalamic area, and ventrolateral portion of the ventromedial hypothalamic nucleus, were devoid of double-labeled cells. Similarly, regions rich in neuroendocrine neurons such as the periventricular hypothalamus and paraventricular and supraoptic hypothalamic nuclei contained no double-labeled cells. These results suggest that modulation of neuroendocrine secretory activity may occur directly at the level of the ME by ER-containing neurons located within restricted regions of the hypothalamus and forebrain. However, the relatively low proportion of ER-containing neurons projecting to the ME suggests that the influence of estradiol upon neuroendocrine function also may include target sites other than the ME.

Animals↗
PubMed1996

Influence of testosterone on LHRH release, LHRH mRNA and proopiomelanocortin mRNA in male sheep.

The mechanism whereby testosterone (T) reduces pulsatile LHRH and LH release is unknown. We tested the hypothesis that hypothalamic levels of LHRH mRNA decrease and proopiomelanocortin (POMC) mRNA increase coincident with reduced LHRH release induced by either long-term or short-term T treatment in male sheep. Experiment 1 examined the effect of long-term T exposure on LHRH and LH release and LHRH and POMC mRNA levels. Yearling Suffolk rams were castrated and assigned to one of four treatments: 1) castrated (n = 4); 2) castrated, portal cannula (n = 5); 3) castrated+T (n = 4) and 4) castrated+T, portal cannula (n = 4). T-treated males received ten 10-cm silastic T-implants immediately after castration. Surgical placement of devices for collecting hypophyseal-portal blood occurred 2 to 3 months after castration. Seven to 10 days after surgery, blood samples were collected at 10-min intervals for 8 h from portal cannulated males or for 5 h from non-cannulated males to assess pulsatile LHRH and/or LH release. Immediately after blood sample collection, hypothalamic tissue was collected for in situ measurement of LHRH or POMC mRNA. T-treatment decreased (P < 0.01) mean LHRH and LH and decreased (P < 0.01) LHRH and LH pulse frequency. T did not significantly affect (P > 0.10) silver grain area per LHRH neuron, but decreased (P < 0.01) silver grain area per POMC neuron. Portal cannulation tended to decrease (P = 0.057) silver grain area per LHRH neuron without significantly affecting (P > 0.10) LHRH cell numbers while reducing (P < 0.01) silver grain area per POMC neuron and POMC cell numbers. A second experiment examined the effect of 72 h of T-infusion on LHRH and POMC mRNA levels. Castrated yearling males were assigned to receive either vehicle (n = 4) or T (768 ug/kg/day; n = 4). Blood samples were collected at 10 min intervals for 4 h prior to and during the final 4 h of infusion. Infusion of T decreased (P < 0.01) mean LH and LH pulse frequency. T did not significantly affect (P > 0.10) silver grain area per LHRH neuron or LHRH cell numbers. T reduced (P < 0.01) silver grain area per POMC neuron without affecting (P > 0.10) POMC cell number. We reject our hypothesis and conclude that reduced LHRH or heightened POMC gene expression are not mechanisms whereby T reduces pulsatile LHRH release in male sheep.

Animals↗
PubMed1996

Differential regulation of luteinizing hormone release by gamma-aminobutyric acid receptor subtypes in the arcuate-ventromedial region of the castrated ram.

We investigated the effects on LH secretion of infusing gamma-aminobutyric acid (GABA) agonists muscimol and baclofen (GABAA and GABAB receptor agonists, respectively) into either the medial preoptic area (mPOA) or the arcuate-ventromedial region (ARC-VMR) of the hypothalamus of castrated rams during the nonbreeding season. Bilateral microdialysis of artificial cerebrospinal fluid for 4 h followed by treatment with artificial cerebrospinal fluid, baclofen (1 mM), or muscimol (1 mM in the ARC-VMR, 250 microM in the mPOA) for 4 h was carried out on three separate occasions in random order. Simultaneously, jugular venous blood was collected at 10-min intervals, and plasma later was assayed for LH. The estimated dose of baclofen delivered to each unilateral microdialysis site was 7.9 micrograms; for muscimol, it was 1.1 micrograms for the mPOA and 4.5 micrograms for the ARC-VMR. In the mPOA, baclofen had no detectable effect, whereas muscimol had a delayed suppressive effect on mean LH (P < 0.01). In the ARC-VMR muscimol rapidly reduced mean LH (P < 0.01). In contrast, baclofen increased mean LH (P = 0.01) and LH pulse amplitude (P = 0.05) without altering the LH interpulse interval (P > 0.10). These results support the involvement of GABAA receptors in the mPOA in regulating LH secretory patterns. More importantly, both GABAA and GABA(B) receptors in the ARC-VMR appear to differentially modulate LH and, presumably, GnRH release. Whether GABA acts directly on the GnRH neuron or indirectly through other neural systems remains to be determined.

Animals↗
PubMed1995

Disruption of reproductive rhythms and patterns of melatonin and prolactin secretion following bilateral lesions of the suprachiasmatic nuclei in the ewe.

To determine whether the photoperiodic responses of reproductive and prolactin (PRL) rhythms in the ewe requires an intact suprachiasmatic nucleus (SCN) driving the pineal rhythm of melatonin secretion, four groups of ovary-intact ewes over a 6-year period were subjected to bilateral (n = 40) or sham lesions (n = 15) of the SCN. Animals were exposed to an alternating 90-120 day photoregimen of 9L:15D and 16L:8D photoperiods. Blood samples taken twice weekly were assayed for prolactin and for progesterone to monitor oestrous cycles. On several occasions blood samples also were taken at hourly intervals for 24 h and analyzed for melatonin. Melatonin concentrations in sham lesioned ewes were basal during the lights-on period and rose robustly during darkness. Those sheep bearing unilateral lesions of the SCN (n = 13) or where the lesion spared the SCN entirely (n = 8) had patterns of melatonin secretion similar to sham ewes. The remaining ewes, having complete (n = 9) or incomplete bilateral (n = 8) destruction of the SCN, with one exception, had disrupted patterns of melatonin secretion. The nature of this disruption varied from complete suppression to continuously elevated levels. In lesioned ewes where melatonin secretion was not affected the onset and cessation of ovarian cycles were similar to sham ewes; stimulation of oestrous cycles under 9L:15D and cessation of oestrous cycles under 16L:8D. In contrast, 13 of 17 ewes with disrupted melatonin secretion also exhibited disrupted patterns of ovarian activity. In these animals oestrous cycles were no longer entrained by photoperiod but still occurred in distinct clusters, that is, groups of cycles began and ended spontaneously. Sheep with normal melatonin patterns showed low levels of PRL secretion during short days and elevated PRL levels during long days. However, 8 of 13 ewes with disrupted melatonin showed patterns of PRL secretion that were no longer entrained by photoperiod. A minority of ewes with disrupted melatonin patterns still showed reproductive (n = 4) and PRL (n = 5) responses similar to those of sham-lesioned ewes. These results show that bilateral destruction of the SCN in the ewe disrupts the circadian pattern of melatonin secretion and that this disruption usually, but not always, is associated with altered photoperiodic responses. These results strongly suggest that the SCN are important neural elements within the photoperiod time-keeping system in this species. A role for the SCN in the generation of endogenous transitions in reproductive activity (refractoriness) and prolactin secretion is not supported.

Animals↗
PubMed1995

Medical outcomes of care for breast cancer among health maintenance organization and fee-for-service patients.

The quality of medical care provided to patients with different types of health insurance coverage has only recently begun to be evaluated. Very few studies have compared the process or outcome of care for cancer. Breast cancer is a good disease to use in medical effectiveness studies because it is relatively easy to diagnose with available technology and is treated effectively if detected early. The primary objectives of this study were to compare type of treatment, stage at diagnosis, and survival for female breast cancer patients newly diagnosed through fee-for-service with third-party coverage or health maintenance organization plans offered by the same medical practice during the same time period. Using a historical cohort design, data from a tumor registry were used to compare type of treatment, stage at diagnosis, and survival for 425 patients diagnosed from 1984 through 1992; 53.6% were members of a health maintenance organization and 46.4% used a variety of fee-for-service plans. Overall, there was no difference between the two groups in type of treatment, stage at diagnosis, or survival. Using fee-for-service as the reference group, Cox regression analysis showed that the unadjusted mortality rate ratio for survival was 0.66 (95% confidence interval = 0.432-1.020), and the rate ratio adjusted for age, race, and stage was 0.80 (95% confidence interval = 0.505-1.257). It was concluded that, despite differences in the type of health insurance coverage, there do not appear to be systematic differences in medical outcomes for breast cancer among women who are treated by the same medical care provider. These findings are of interest in the context of the rapidly changing organization of medical care with its implications for clinical practice and for the quality of care offered to patients with different types of medical insurance coverage.

Adult↗
PubMed1994

A survey of physician beliefs and self-reported practices concerning screening for early detection of cancer.

Cancer is the second leading cause of death in the United States. Early detection of cancer greatly improves 5-year survival for many sites, and in 1980 the American Cancer Society (ACS) published recommendations for performing cancer screening with the goal of promoting early cancer detection in asymptomatic persons. This cross-sectional survey examined beliefs and practices related to six cancer screening tests and procedures in a group of 68 primary care physicians in a multi-specialty group practice in Houston, Texas. Constructs from the Health Belief Model and Social Cognitive Theory were used to identify factors that might influence performance of cancer screening. Physicians in this study reported greater compliance with ACS recommendations for performance than has been found in other studies, and there is an indication that some screening tests may be performed even when not indicated based on age-specific criteria. Respondents reported performing digital rectal examination, stool occult blood testing, and sigmoidoscopy more frequently in men than in women. No belief factor emerged as being associated with performance of all screening procedures, and associations that were noted for some procedures were not consistent across patient age and gender groups. Some possible directions for further research and development of programs to promote the appropriate and cost effective use of cancer screening are physician education to include information about age and gender appropriate guidelines for screening and opportunities for skills training and practice workshops for some procedures.

Adult↗
PubMed1994

Effect of inhibiting 5 alpha-reductase activity on the ability of testosterone to inhibit luteinizing hormone release in male sheep.

The extent to which inhibitory effects of testosterone (T) on LH secretion in the ram are mediated by its metabolite dihydrotestosterone (DHT) is unknown. Our objective was to determine the effect of inhibiting 5 alpha-reductase activity on pulsatile patterns of LH release in castrated, T-treated male sheep. Nine Dorset and six Hampshire castrated male sheep were allocated equally to one of three treatment groups: 1) infusion of T (768 micrograms/kg/day), 2) infusion of the reductase inhibitor (RI) L-651,723 (0.6 mg/kg/day), and 3) T+RI infusion. Treatments were continuously infused for 3 days. Blood samples were collected via an indwelling jugular catheter at 10-min intervals for 4 h immediately prior to (Day 0) and during the final 4 h of infusion (Day 3). Changes in mean LH, LH pulse amplitude, LH interpulse interval (IPI), T, 17 beta-estradiol (E), and DHT were derived for each animal by subtracting values for Day 0 from Day 3. Data were subjected to one-way analysis of variance. The increase in T and E after infusion of T was similar (p > 0.10) in T- and T+RI-treated males and greater (p < 0.01) than in RI-treated males. The increase of DHT was greater (p < 0.01) in T-treated than either T+RI- or RI-treated males whereas the change was similar (p > 0.10) for T+RI- and RI-treated males. T decreased mean LH more (p < 0.01) than RI. T+RI suppressed mean LH more (p < 0.01) than RI but not as much (p < 0.01) as T alone.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1994

Differential actions of phospholipase C on gonadotropin-releasing-hormone-stimulated release and glycosylation of luteinizing hormone in rat anterior pituitary cells.

Receptor-mediated activation of phospholipase C (PLC) which releases diacylglycerol and inositol trisphosphate has been implicated in the action of gonadotropin-releasing hormone (GnRH) on gonadotrophs. Previously we demonstrated that the synthetic diacylglycerol, phorbol 12-myristate 13-acetate (PMA) and PLC mimic the stimulatory effects of GnRH on both luteinizing hormone (LH) glycosylation and release. In this study we further investigated how PMA or PLC interact with GnRH to control LH release versus glycosylation. Cultured pituitary cells were incubated in the presence of radiolabeled precursors and GnRH (0, 1, or 100 nM), with or without PMA (10 nM) or PLC (0.24 U/ml) for 4 h. LH translation and glycosylation were monitored by measuring incorporation of [14C]alanine and [3H]glucosamine, respectively, into total (cell and medium) immunoprecipitable LH. Immunoreactive LH (IRLH) was measured by radioimmunoassay. Both PMA and PLC increased (p < 0.01) basal IRLH release, and IRLH release stimulated by 1 nM GnRH. Neither PMA nor PLC exerted an additive effect on IRLH release stimulated by 100 nM GnRH. The interactions between PMA or PLC and GnRH on IRLH release were significant (p < 0.01). Both PMA and PLC elevated (p < 0.01) total [3H]glucosamine-LH, but had no additive effect with 1 nM GnRH; PLC depressed (p < 0.05) the stimulatory effect of 100 nM GnRH, whereas PMA had no effect. The interactions between PMA or PLC and GnRH on LH glycosylation were significant (p < 0.01). PMA, PLC or GnRH alone did not affect total [14C]alanine-LH. In the presence of 1 or 100 nM GnRH, PLC, but not PMA, decreased (p < 0.05) total [14C]alanine-LH.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1994

Effect of anterior hypothalamic area lesions on photoperiod-induced shifts in reproductive activity of the ewe.

The areas of the brain involved in photoperiodic control of reproduction are not well defined. The objective of this study was to determine whether anterior hypothalamic area (AHA) lesions in the ewe affected the responses of the reproductive system to shifts in the length of the daily photoperiod and development of photorefractoriness to a constant short day photoperiod. Eleven intact ewes received bilateral radiofrequency lesions of the AHA (AHAX), and five received sham lesions (sham). The ewes then were placed in photochambers and exposed alternately to two approximately 90-day periods of long [16 h of light, 8 h of darkness (16L:8D)] and short (10L:14D) days and then to 10L:14D for an additional 165 days. Blood samples were collected twice weekly to monitor plasma profiles of progesterone, PRL, and total T4, and during the second 16L:8D photoperiod, hourly for one 24-h period to assess melatonin release. Lesions increased (P < 0.001) the interval between the start of long days and cessation of estrous cycles during both long day periods, but did not affect the interval between the start of short days and the onset of estrous cycles for either the first (P = 0.08) or second (P > 0.10) short day period. Consequently, the durations of both anestrous periods were shorter (P < 0.001) for AHAX than for sham ewes. AHA lesions did not affect (P > 0.10) diurnal patterns of melatonin release. No effects (P > 0.10) of lesions were evident on plasma patterns of PRL or total T4 for any short or long day photoperiod. Development of photorefractoriness to constant short days either did not occur or was markedly delayed in five of nine AHAX (P < 0.01) ewes, whereas the other four AHAX ewes became refractory at a time similar (P > 0.10) to that in sham ewes. Responses to inhibitory long day photoperiods and constant short days were highly (P < 0.05) correlated (r = 0.74) and appeared dependent upon the extent of the AHA lesion. These results suggest that AHA lesions disrupt neuronal pathways mediating the effects of shifts in photoperiod on reproductive activity and development of photorefractoriness to constant short days. Our results suggest that the effects of AHA lesions are confined to the termination of reproductive activity, and that different neural pathways participate in photostimulation vs. photosuppression or photorefractoriness.

Animals↗
PubMed1993

A re-evaluation of the effects of gonadal steroids on neuronal activity in the male rat.

Single unit activity (SUA) was recorded from 77 cells located in the arcuate nucleus (ARC) and medial preoptic area (MPA) of anesthetized, intact male rats. Animals were administered vehicle, testosterone (T; 5 or 50 micrograms) or 17 beta-estradiol (E; 0.5 microgram) intravenously and SUA was monitored for 8-12 min. T (50 micrograms) reduced SUA in 50% of ARC units and 44% of MPA units within 2.1 +/- 0.46 and 3.3 +/- 0.92 min, respectively. Inhibition of ARC SUA was more pronounced than MPA SUA. A small percentage (9%) of ARC units were excited by T. E reduced SUA in 29% of ARC units and 27% of MPA units. Single doses of 5 micrograms T did not affect ARC activity. However, when followed within 10 min by an additional dose of 5 or 50 micrograms T, 30% and 43% of ARC units were inhibited, respectively. Doses (10 micrograms) of T produced plasma T concentrations within physiological limits, although 50 micrograms doses produced supraphysiological T levels. Neither dose affected circulating LH concentrations. We conclude that physiological and supraphysiological concentrations of T can rapidly affect SUA within the ARC.

Analysis of Variance↗