Pituitary Gonadotropin-Releasing Hormone Receptors During the Rat Estrous Cycle

Savoy‐Moore, Ruth T.; Schwartz, Neena B.; Duncan, Joyce A.; Marshall, John C.

doi:10.1126/science.6250218

Cited by 251 publications

(102 citation statements)

References 27 publications

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“…The first surge represents the short functional life of the corpus luteum, while the second is the preovulatory surge of P in the evening of the proestrus. The patterns of E 2 and P secretion during the 4 day estrous cycle are in agreement with previous studies, although different bloodcollection procedures were used (Butcher et al 1974, Smith et al 1975, Savoy-Moore et al 1980. In previous studies, blood was collected by decapitation, while we used the same animal in each estrous cycle phase by sampling blood through jugular cannulation.…”

Section: Discussionsupporting

confidence: 70%

Neonatal handling and reproductive function in female rats

Gomes¹,

Raineki²,

Paula³

et al. 2005

Journal of Endocrinology

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Neonatal handling induces anovulatory estrous cycles and decreases sexual receptivity in female rats. The synchronous secretion of hormones from the gonads (estradiol (E 2 ) and progesterone (P)), pituitary (luteinizing (LH) and follicle-stimulating (FSH) hormones) and hypothalamus (LH-releasing hormone (LHRH)) are essential for the reproductive functions in female rats. The present study aimed to describe the plasma levels of E 2 and P throughout the estrous cycle and LH, FSH and prolactin (PRL) in the afternoon of the proestrus, and the LHRH content in the medial preoptic area (MPOA), median eminence (ME) and medial septal area (MSA) in the proestrus, in the neonatal handled rats. Wistar pup rats were handled for 1 min during the first 10 days after delivery (neonatal handled group) or left undisturbed (nonhandled group). When they reached adulthood, blood samples were collected through a jugular cannula and the MPOA, ME and MSA were microdissected. Plasma levels of the hormones and the content of LHRH were determined by RIA. The number of oocytes counted in the morning of the estrus day in the handled rats was significantly lower than in the nonhandled ones. Neonatal handling reduces E 2 levels only on the proestrus day while P levels decreased in metestrus and estrus. Handled females also showed reduced plasma levels of LH, FSH and PRL in the afternoon of the proestrus. The LHRH content in the MPOA was significantly higher than in the nonhandled group. The reduced secretion of E 2 , LH, FSH and LHRH on the proestrus day may explain the anovulatory estrous cycle in neonatal handled rats. The reduced secretion of PRL in the proestrus may be related to the decreased sexual receptiveness in handled females. In conclusion, early-life environmental stimulation can induce long-lasting effects on the hypothalamus-pituitary-gonad axis .

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Section: Discussionsupporting

confidence: 70%

Neonatal handling and reproductive function in female rats

Gomes¹,

Raineki²,

Paula³

et al. 2005

Journal of Endocrinology

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“…gonadotropes. GnRH pulses are slower during diestrus, thereby favoring FSH synthesis, but faster during proestrus, favoring LH secretion [157][158][159].…”

Section: Gonadotropin Releasing Hormone (Gnrh)mentioning

confidence: 99%

Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

2011

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Leptin, a potent anorexigenic hormone secreted primarily by adipocytes, is known to be expressed in the anterior pituitary. Studies in our laboratory found leptin proteins and mRNA predominantly in somatotropes in normal male and cycling female rats. In contrast, leptin expression predominated in gonadotropes during pregnancy and lactation. Leptin expression varied with the cycle and was enhanced, in vitro by gonadotropin releasing hormone and Neuropeptide Y. In contrast, ghrelin inhibited pituitary leptin expression. Pituitary leptin in somatotropes or gonadotropes was reduced by nutritional deprivation for 24 h. However, growth hormone (GH), luteinizing hormone (LH) and pituitary leptin recovered if fasted animals were given glucose water. The glucose-mediated recovery suggests that the system is sensitive to changes in serum glucose. Somatotropes and gonadotropes also recovered if pituitary cells from fasted rats were stimulated in vitro with 1-100 pg/ml leptin. This in vitro leptin-mediated recovery suggests that leptin is important in the maintenance of somaotropes and gonadotropes. Collectively, the data suggest that pituitary leptin might serve as a "glucostat", sensing levels of serum glucose and reporting this nutritional state to somaotropes and gonadotropes in a paracrine manner. A decrease in pituitary leptin might signal nutritional deprivation to somatotropes and gonadotropes, lowering LH and GH production and allowing for conservation of resources. Lower GH would help conserve fat stores and lower LH would promote survival over reproduction.

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“…The responsiveness of the gonadotrophs to LH-RH varies under different conditions, depending on the hormonal milieu (4,5), and seems to be correlated at least in part with the number of LH-RH receptors (6,7). The regulation of the number and the responsiveness of LH-RH-Rs is complex, being influenced by gonadal steroids, inhibin, and gonadotropins, as well as by its own ligand, LH-RH (5,(8)(9)(10)). An intermittent administration of native LH-RH or LH-RH agonists in vivo and in vitro, mimicking the natural pulsatile release of this neuropeptide from the hypothalamus, stimulates the synthesis and the release of gonadotropins and leads to an increase in the number of its receptors (11).…”

mentioning

confidence: 99%

Luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix down-regulates the mRNA expression of pituitary receptors for LH-RH by counteracting the stimulatory effect of endogenous LH-RH

Kovacs¹

2001

Proceedings of the National Academy of Sciences

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The mechanisms through which LH-RH antagonists suppress gonadotroph functions and LH-RH receptor (LH-RH-R) production are incompletely understood. To elucidate these mechanisms, we investigated the effects of Cetrorelix on the mRNA expression of pituitary LH-RH-R and luteinizing hormone (LH) secretion in three experimental systems with different pituitary LH-RH environments. Ovariectomy induced 3.61-fold and 6.34-fold increases in the mRNA expression of pituitary LH-RH-R in rats after 11 and 21 days, respectively. After (5 h) a single injection of 100 g Cetrorelix, no significant decrease occurred in the mRNA levels of pituitary LH-RH-R in ovariectomized (OVX) rats with high pituitary exposure to LH-RH, but there was a significant 23.2% reduction in cycling rats with normal hypophysial LH-RH environment. Prolonged treatment for 10 days with a Cetrorelix depot formulation releasing 100 g͞day decreased the concentration of mRNA for pituitary LH-RH-R by 72.6% in OVX rats, but only by 32.9% in normal rats. The decline in serum LH was 98.7% in OVX rats and 63.2% in normal rats, resulting in a minimal 0.1-0.2 ng͞ml LH concentration in both groups. A continuous exposure of pituitary cells to 100 nM Cetrorelix in the superfusion system, which is devoid of LH-RH, did not cause any significant changes in LH-RH-R mRNA level. These studies demonstrate that prolonged exposure to Cetrorelix in vivo, but not in vitro, down-regulates the mRNA expression of the pituitary receptors for LH-RH. Our findings indicate that LH-RH antagonists exert their inhibitory effects on the gene expression of pituitary LH-RH-R by counteracting the stimulatory effect of endogenous LH-RH.T he hypothalamic decapeptide LH-RH plays a pivotal role in regulating luteinizing hormone (LH) and follicle-stimulating hormone secretion through the activation of high-affinity G protein-coupled receptors on the plasma membrane of pituitary gonadotrophs (1-3). The responsiveness of the gonadotrophs to LH-RH varies under different conditions, depending on the hormonal milieu (4, 5), and seems to be correlated at least in part with the number of LH-RH receptors (6, 7). The regulation of the number and the responsiveness of LH-RH-Rs is complex, being influenced by gonadal steroids, inhibin, and gonadotropins, as well as by its own ligand, LH-RH (5, 8-10). An intermittent administration of native LH-RH or LH-RH agonists in vivo and in vitro, mimicking the natural pulsatile release of this neuropeptide from the hypothalamus, stimulates the synthesis and the release of gonadotropins and leads to an increase in the number of its receptors (11). However, continuous administration of LH-RH and its agonists, especially at high concentration, causes a downregulation of receptors and desensitization of gonadotrophs (11-13). Thus, administration of depot preparations of LH-RH agonists results in the suppression of the secretion of gonadotropins and sex hormones which provides the basis for clinical applications of this class of compounds (1, 2, 14).In the past 25 years, more ...

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Pituitary Gonadotropin-Releasing Hormone Receptors During the Rat Estrous Cycle

Cited by 251 publications

References 27 publications

Neonatal handling and reproductive function in female rats

Neonatal handling and reproductive function in female rats

Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

Luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix down-regulates the mRNA expression of pituitary receptors for LH-RH by counteracting the stimulatory effect of endogenous LH-RH

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