Browsing by Subject "LH"

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Changes in GRK3 and Norepinephrine Responsiveness in Locus Coeruleus Neurons are Associated with Learned Helplessness After Repeated Forced Swim Stress
(2012-04-19) Saha, Kaustuv; EIKENBURG, DOUGLAS C.; KNOLL, BRIAN; ZIBURKUS, JOKUBAS; STANDIFER, KELLY M.; LAU, YUEN-SUM
In brain, locus coeruleus plays an important role in mediating the stress responses. Two important neurotransmitter/hormones released in locus coeruleus (LC) during exposure to stress include corticotrophin releasing factor (CRF) and norepinephrine (NE). CRF and NE predominantly act on G protein-coupled receptors (GPCR), the corticotrophin-releasing factor type 1 receptor (CRF1-R) and the alpha2A–adrenoceptors (α2A-AR), respectively. Activation of CRF1-R increases LC neuronal firing and activation of postsynaptic α2A-AR inhibits firing of LC neurons. Additionally, presynaptic α2A-ARs act as autoreceptors inhibiting release of NE in LC. Both the agonist-occupied CRF1-R and α2A-AR are preferentially desensitized by G protein-coupled receptor kinase 3 (GRK3). This desensitization contributes to termination of the signaling of CRF1-R and α2A-AR, observed during the persistent presence of neurotransmitters during stress. At present, there is a gap in knowledge as to what changes in GPCR signaling occur during single and repeated stress. The present study provides a contribution towards filling this gap. This study observed the effects of single and repeated forced swim stress on the escape task performance of rats in a shuttle-box. The study also observed the effects of GRK3 and NE responsiveness in LC neurons in slices of rat brainstem. Both single and repeated forced swim stress segregated the stressed rats into two clusters based on their performance in the escape task. One cluster showed impaired escape behavior compared to controls and was designated Learned Helpless (LH), showing susceptibility to the adverse effects of stress. The other cluster of stressed rats showed escape behavior similar to the controls and was termed Non-Helpless (NH), showing resilience against the adverse consequences of stress. Thus this study demonstrated that a milder stress than inescapable electric shock, the stress paradigm of forced swim, could induce deficits in escape behavior. These deficits are a well-established index of depression-associated behavior. Biochemical analysis showed that single forced swim stress did not cause any change in the levels of GRK3, CRF1-R and α2A-AR in the LC of the LH rats compared to the control and NH rats. However, repeated forced swim stress caused a decrease in the levels of GRK3 and an increase in the levels of CRF1-R and α2A-AR in the LC of LH rats compared to the control and NH rats. Also, repeated forced swim stress was accompanied by an increase in the responsiveness of α2A-AR upon application of lower concentrations of NE as observed by measuring the changes in membrane current in response to different concentrations of NE in single LC neuron. Moreover, the increases in immobility, LH behavior, decreases in GRK3 and increase in CRF1-R and α2A-AR in LC after repeated forced swim stress alone were not observed in rats pretreated with desipramine (DMI). In conclusion, a much milder and more physiological stressor than electric shock, repeated forced swim stress, enables the identification of a sub-population of stress-susceptible rats that display LH. This LH behavior was associated with a decrease in GRK3 and an increase in α2A-AR levels and responsiveness in LC, accompanied by an increase in CRF1-R levels. The repeated forced swim-induced changes in responsiveness of the postsynaptic α2A-AR may indicate that when the stressful stimuli are removed there is a rebound compensatory mechanism by which the α2A-AR may reduce LC hyperactivity. Although, the method used in this study measured only postsynaptic α2A-AR function, if similar changes in the presynaptic α2A-AR occur, this would decrease NE release in LC during stress. Thus the pre- and postsynaptic α2A-ARs would cancel each other functionally. This would lead to predominance of excitatory effects of CRF1-R, potentially contributing to the hyperresponsiveness of LC to CRF and to hyperactivity of the LC that is characteristically observed on exposure to stress. DMI pretreatment, by increasing the availability of norepinephrine in the LC, will maintain an inhibitory tone on the neurons and prevent the hyperactivity of LC neurons associated with exposure to repeated stress. This will lead to prevention of repeated forced swim stress-induced decrease in GRK3 and increase in the levels and responsiveness α2A-AR and CRF1-Rs in the LC, resulting in the prevention of subsequent impairment of escape behavior in rats.
Endogenous Cortisol, Luteinizing Hormone, and Testosterone Secretion and GnRH-induced Luteinizing Hormone and Testosterone Secretion in Prenatally Stressed Sexually Mature Brahman Bulls
(2014-12-12) Littlejohn, Brittni Paige
The purpose of this experiment was to determine the effects of prenatal transportation stress (PNS) on LH, testosterone, and cortisol secretion before and after GnRH stimulation in sexually mature Brahman bulls. Forty-eight Brahman cows were exposed to a transportation event at 5 stages of gestation (and 48 cows were non-transported controls). Bulls from these cows were electroejaculated every 2 wk beginning at a scrotal circumference of 24 cm through sexual maturity (i.e., 500 million sperm/ejaculate). The initial 11 control and 12 PNS bulls to reach sexual maturity were selected for endocrine evaluation. Within 7-21 d after reaching sexual maturity, bulls were fitted with jugular cannulas, and blood samples were collected at 15-min intervals for 6 h. Exogenous GnRH was then administered intravenously (10 ng/kg BW) and blood collection continued at 15-min intervals for an additional 8 h. Concentrations of LH, testosterone, and cortisol in serum were determined. Amplitude and maximum concentration of a detectable LH pulse and testosterone response, baseline concentration, average concentration in the h prior to GnRH administration, and area under the curve were calculated for LH and testosterone in the 4-h period immediately preceding and 6-h period immediately following GnRH administration. Cortisol in the h prior to GnRH administration and area under the curve were calculated for the 4-h period immediately preceding GnRH administration. Duration of the GnRH-induced LH release was determined. More PNS (10 of 11) than control (3 of 12) bulls exhibited an LH pulse prior to GnRH administration (P<0.01). More PNS bulls exhibited an endogenous testosterone response to endogenous LH secretion (9 of 11; P=0.02) relative to control bulls (4 of 12). In the h preceding GnRH administration, testosterone was greater (P=0.0064) in PNS compared to control bulls, and cortisol was lower in PNS compared to control bulls. No other characteristic associated with the release of LH, testosterone, or cortisol secretion prior to GnRH administration differed between groups (P>0.1). Bulls responded similarly to exogenous GnRH, except duration of GnRH-induced LH release which was greater (P=0.02) in PNS (268?18 min) relative to control (207?16 min) bulls. Prenatal stress affected postnatal secretion of LH, testosterone, and cortisol in sexually mature Brahman bulls.
Reproductive neuroendocrine function in the mare as reflected in the intercavernous sinus during ovulatory, anovulatory, and transitional seasons
(Texas A&M University, 2006-08-16) Cooper, Dee A
We hypothesized that marked reductions in secretion of luteinizing hormone (LH) during transitional and anovulatory periods can be accounted for by similar reductions in hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Catheters were inserted surgically into the intercavernous sinus (ICS) of seven non-pregnant mares via the superficial facial vein during the ovulatory season (August 12-23), fall transition (November 15-30), the anovulatory season (January 19 - February 1) and spring transition (March 24 - May 12). Catheter placement was confirmed and standardized in each mare by lateral radiography. Ovarian status was monitored throughout the study by transrectal ultrasonography and serum concentrations of progesterone. During the breeding season, ICS blood samples were collected at 5-min intervals for 8 h when the dominant follicle reached approximately 35 mm and estrous behavior was observed. All mares ovulated within 5 d after sampling, except one mare who ovulated < 24 h before sampling. During the fall, mares were anovulatory (n = 5) or had a final ovulation within 5 d following intensive sampling (n = 2). Winter anovulation sampling was performed when all mares were anovulatory. During spring transition, each mare was sampled just before the second ovulation of the season. Similar to the ovulatory season, mares were sampled when the dominant, preovulatory follicle reached approximately 35 mm and estrous behavior was observed. Mean concentrations of LH were markedly higher (P < 0.01) during the breeding season than during all other seasons. Lower mean concentrations of LH in the fall transition, winter anovulation and spring transition sampling periods occurred coincident with a similar reduction (P < 0.01) in amplitude of LH pulses. Unexpectedly, neither the frequency (pulse/8 h) of LH pulses, frequency and amplitude of GnRH pulses, nor mean concentrations of GnRH differed among seasons. In addition, there were no differences observed due to season in mean concentrations of FSH or amplitude of FSH pulses. However, a small but significant (P < 0.05) reduction in the frequency of FSH pulses was observed during fall transition compared to all other seasons. In summary, contrary to accepted dogma, these results indicate that the photoperiodic initiation of seasonal anovulation in the mare is mediated at the level of the anterior pituitary, and appears to occur through a dampening of gonadotroph responsiveness to an unchanging pattern and magnitude of GnRH secretion.
Role of an Equine Homologue of Gonadotropin-Inhibiting Hormone in Controlling Sectretion of Luteinizing Hormone in the Mare
(2012-07-16) Prezotto, Ligia Dias
Four experiments were conducted to test the hypothesis that RF-amide related peptide 3 (RFRP3) negatively regulate the secretion of LH in mares. In Exp. 1, mares received native gonadotropin-releasing hormone (GnRH) continuously at a rate of 20 microgram/h, delivered subcutaneously using Alzet osmotic pumps during the luteal phase of the estrous cycle. Mares were treated with i.v. bolus injections of 0, 500 and 1,000 microgram eRFRP3 on days 4, 6 and 8 of cycle. Mean concentrations of LH in the peripheral circulation averaged 1.2 +/- 0.2 ng/mL and did not differ among groups before or following RFRP3 treatment. In Exp. 2, pituitary venous effluent was sampled for characterization of episodic release of LH. Mares received either saline or eRFRP3 (250 microgram) i.v. every 10 min for 6 h beginning 2 h after onset of sampling. At hour 6, each mare was challenged with 1 mg GnRH. Neither mean ICS concentrations of LH (1.3 +/- 0.2 ng/ml), nor frequency (3.6 +/- 0.55 episodes/h), amplitude (0.2 +/- 0.03 ng/ml), or duration (36.3 +/- 3.5 min) of individual secretory episodes, differed between groups before or after eRFRP3 treatment. Area under the GnRH-induced LH curve (arbitrary units) also did not differ between control and RFRP3 treated mares (175.9 +/- 11.4 vs. 192.6 +/- 10.6). In Exp. 3, winter anovulatory mares (n=6) were treated continuously for 7 d with GnRH (100 microgram/h) to stimulate synthesis of LH and increase circulating concentrations of LH to values similar to the breeding season. The ICS was catheterized for blood sampling and mares were treated with saline or RFRP3 (5 mg) in a replicated Latin square design. Treatment with RFRP3 failed to alter ICS mean concentration of LH (0.95 +/- .03 ng/ml). Finally in Exp. 4, mares in the follicular phase of the estrous cycle were assigned randomly to receive either saline (n=3) or 10 microgram/kg BW of oRFRP3 (n=3) in a single injection. No effect on mean concentration of LH was observed. In contrast to observations in birds and other mammals, results of the current experiments fail to provide evidence for functional activity of eRFRP3 or oRFRP3 in regulating LH release in the mare.
Role of leptin in regulating the bovine hypothalamic-gonadotropic axis
(Texas A&M University, 2004-09-30) Amstalden, Marcel
The physiological mechanisms through which nutrition mediates its effects in controlling reproduction are not well characterized. Both neural and endocrine components have been implicated in the communication of nutritional status to the central nervous system. Leptin, a hormone synthesized and secreted mainly by adipocytes, is heavily involved in this communication network. The objectives of studies reported herein were 1) to determine the effects of short-term restriction of nutrients on circulating leptin, leptin gene expression in adipose tissue, and leptin receptor (LR) gene expression in the adenohypophysis of ovariectomized cows; and 2) to investigate the responsiveness of the hypothalamic-adenohypophyseal (AP) axis of fasted and non-fasted cattle to leptin. Studies demonstrated that circulating concentrations of leptin and leptin gene expression in subcutaneous adipose tissue are decreased by fasting. Although 2 to 3 days of fasting did not affect patterns of release of luteinizing hormone (LH), cerebroventricular infusions of leptin increased mean circulating concentrations of LH in fasted, but not normal-fed cows, without affecting frequency or amplitude of pulses of LH. In vitro studies were conducted to determine whether the in vivo effects of leptin could be accounted for at the hypothalamic and/or AP levels. Leptin did not affect the release of gonadotropin-releasing hormone (GnRH) from hypothalamic-infundibular explants from either normal-fed or fasted cattle. Moreover, leptin did not affect the basal release of LH from bovine AP cells or AP explants from normal-fed cows. However, leptin induced a higher basal release of LH from AP explants of fasted cows and increased GnRH-stimulated release of LH from AP explants of normal-fed cows. Results demonstrate that leptin acts directly at the AP level to modulate the secretion of LH, and its effects are dependent upon nutritional status. Cellular mechanisms associated with the increased responsiveness of gonadotropes to leptin in fasted cows were investigated. Expression of LR and suppressor of cytokine signaling-3 (SOCS-3) in the adenohypophysis did not account for the increased responsiveness of fasted cows to leptin. Therefore, although leptin clearly stimulates the hypothalamic-gonadotropic axis in nutrient-restricted cattle, it is unclear why cattle maintained under neutral or positive energy balance are resistant to leptin.

Browsing by Subject "LH"

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