Hypothesis testing of the aging male gonadal axis via a biomathematical construct

2001 ◽  
Vol 280 (6) ◽  
pp. R1755-R1771 ◽  
Author(s):  
Daniel M. Keenan ◽  
Johannes D. Veldhuis
Keyword(s):  
Luteinizing Hormone ◽  
Gonadotropin Releasing Hormone ◽  
Computer Assisted ◽  
Aging Male ◽  
Aging Men ◽  
Model Predictions ◽  
Feedback Networks ◽  
Lh Secretion ◽  
Appl Math ◽  
Dynamic Ensembles

Neuroendocrine axes are feedback- and feedforward-coupled dynamic ensembles. Disruption of selected pathways in such networklike organizations may explicate loss of orderly hormonal output as observed in aging. To test this notion more explicitly, we implemented an earlier computer-assisted biomathematical model of the interlinked male hypothalamo [gonadotropin-releasing hormone (GnRH)]-pituitary [luteinizing hormone, (LH)]-testicular [Leydig cell testosterone (Te)] axis ( Am J Physiol Endocrinol Metab Physiol 275: E157–E176, 1988; Keenan D., W. Sun, and J. D. Veldhuis, SIAM J Appl Math 61: 934–965, 2000). Thereby, we appraise mechanistic hypotheses for more disorderly LH and Te secretion in aging men. We compare model predictions with monitored abnormalities in the older male, namely, irregular patterns of individual and synchronous LH and Te release, reduced 24-h rhythmic Te output, and variably elevated LH secretion. Among the mechanisms examined, the most parsimonious aging hypothesis would entail impaired LH feedforward on Te without or with attenuated Te feedback on GnRH/LH secretion. This investigative strategy should aid in exploring new postulates of disrupted feedback networks in pathophysiology.

scholarly journals Induction of final oocyte maturation in Cyprinidae fish by hypothalamic factors: a review

2009 ◽  
Vol 54 (No. 3) ◽  
pp. 97-110 ◽  
Author(s):  
P. Podhorec ◽  
J. Kouril
Keyword(s):  
Luteinizing Hormone ◽  
Oocyte Maturation ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
Gonadotropin Releasing Hormone ◽  
Luteinizing Hormone Secretion ◽  
Releasing Hormone ◽  
Final Oocyte Maturation ◽  
In Captivity ◽  
Lh Secretion

Gonadotropin-releasing hormone in Cyprinidae as in other Vertebrates functions as a brain signal which stimulates the secretion of luteinizing hormone from the pituitary gland. Two forms of gonadotropin-releasing hormone have been identified in cyprinids, chicken gonadotropin-releasing hormone II and salmon gonadotropin-releasing hormone. Hypohysiotropic functions are fulfilled mainly by salmon gonadotropin-releasing hormone. The only known factor having an inhibitory effect on LH secretion in the family Cyprinidae is dopamine. Most cyprinids reared under controlled conditions exhibit signs of reproductive dysfunction, which is manifested in the failure to undergo final oocyte maturation and ovulation. In captivity a disruption of endogenous gonadotropin-releasing hormone stimulation occurs and sequentially that of luteinizing hormone, which is indispensible for the final phases of gametogenesis. In addition to methods based on the application of exogenous gonadotropins, the usage of a method functioning on the basis of hypothalamic control of final oocyte maturation and ovulation has become popular recently. The replacement of natural gonadotropin-releasing hormones with chemically synthesized gonadotropin-releasing hormone analogues characterized by amino acid substitutions at positions sensitive to enzymatic degradation has resulted in a centuple increase in the effectiveness of luteinizing hormone secretion induction. Combining gonadotropin-releasing hormone analogues with Dopamine inhibitory factors have made it possible to develop an extremely effective agent, which is necessary for the successful artificial reproduction of cyprinids.

scholarly journals Galanin Enhancement of Gonadotropin-Releasing Hormone-Stimulated Luteinizing Hormone Secretion in Female Rats Is Estrogen Dependent

Endocrinology ◽  
2003 ◽  
Vol 144 (2) ◽  
pp. 484-490 ◽  
Author(s):  
Cynthia L. Splett ◽  
Joseph R. Scheffen ◽  
Joshua A. Desotelle ◽  
Vicky Plamann ◽  
Angela C. Bauer-Dantoin
Keyword(s):  
Luteinizing Hormone ◽  
Hormone Secretion ◽  
Gonadotropin Releasing Hormone ◽  
Gonadal Steroids ◽  
Female Rats ◽  
Luteinizing Hormone Secretion ◽  
Ovx Rats ◽  
Lh Secretion ◽  
Lines Of Evidence

The hypothalamic peptide GnRH is the primary neuroendocrine signal regulating pituitary LH in females. The neuropeptide galanin is cosecreted with GnRH from hypothalamic neurons, and in vitro studies have demonstrated that galanin can act at the level of the pituitary to directly stimulate LH secretion and also augment GnRH-stimulated LH secretion. Several lines of evidence have suggested that the hypophysiotropic effects of galanin are important for the generation of preovulatory LH surges. To determine whether the pituitary actions of galanin are enhanced by the preovulatory steroidal milieu, LH responses to galanin administration (with or without GnRH) were examined in: 1) ovariectomized (OVX); 2) OVX, estrogen (E)-primed; and 3) OVX, E- and progesterone-treated female rats. Results from the study indicate that galanin enhances GnRH-stimulated LH secretion only in the presence of E (in OVX, E-primed, or E- and progesterone-treated rats). Galanin alone does not directly stimulate LH secretion under any of the steroid conditions examined. In the absence of gonadal steroids (OVX rats), galanin inhibits GnRH-stimulated LH secretion. These findings suggest that the primary pituitary effect of galanin is to modulate GnRH-stimulated LH secretion, and that the potentiating effects of galanin occur only in the presence of E.

scholarly journals Effects of Central Injection of Anti-LPS Antibody and Blockade of TLR4 on GnRH/LH Secretion during Immunological Stress in Anestrous Ewes

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Karolina Haziak ◽  
Andrzej Przemysław Herman ◽  
Dorota Tomaszewska-Zaremba
Keyword(s):  
Luteinizing Hormone ◽  
Anterior Pituitary ◽  
Gonadotropin Releasing Hormone ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Immune Stress ◽  
Immunological Stress ◽  
Lh Release ◽  
Lh Secretion ◽  
Tlr4 Receptor

The present study was designed to examine the effect of intracerebroventricular (icv) administration of antilipopolysaccharide (LPS) antibody and blockade of Toll-like receptor 4 (TLR4) during immune stress induced by intravenous (iv) LPS injection on the gonadotropin-releasing hormone/luteinizing hormone (GnRH/LH) secretion in anestrous ewes. Injection of anti-LPS antibody and TLR4 blockade significantly (P < 0.01) reduced the LPS dependent lowering amount ofGnRHmRNA in the median eminence (ME). Moreover, blockade of TLR4 caused restoration ofLH-βtranscription in the anterior pituitary decreased by the immune stress. However, there was no effect of this treatment on reduced LH release. The results of our study showed that the blockade of TLR4 receptor in the hypothalamus is not sufficient to unblock the release of LH suppressed by the immune/inflammatory challenges. This suggests that during inflammation the LH secretion could be inhibited directly at the pituitary level by peripheral factors such as proinflammatory cytokines and circulating endotoxin as well.

Estrogen inhibition of LH and FSH secretion: effects of a GnRH antagonist

1986 ◽  
Vol 250 (4) ◽  
pp. E341-E345
Author(s):  
M. C. Charlesworth ◽  
N. B. Schwartz
Keyword(s):  
Luteinizing Hormone ◽  
Negative Feedback ◽  
Gnrh Antagonist ◽  
Follicle Stimulating Hormone ◽  
Estradiol Benzoate ◽  
Gonadotropin Releasing Hormone ◽  
Ovariectomized Rats ◽  
Inhibitory Effects ◽  
Dependent Component ◽  
Lh Secretion

Follicle-stimulating hormone (FSH) levels are not suppressed as rapidly or to the same degree as luteinizing hormone (LH) levels in ovariectomized rats treated with either gonadotropin-releasing hormone (GnRH) antagonist or estrogen. The acute inhibitory effects of various doses of estrogen on FSH and LH secretion were examined in cannulated, 2-wk ovariectomized rats. No dose of 17 beta-estradiol, up to 2,500 ng injected intravenously, suppressed FSH, although LH secretion was inhibited 50% within 1 h by 100 ng. In another experiment, estradiol benzoate (EB; 10 or 250 micrograms; sc injection in oil) was only marginally effective in suppressing FSH, compared with LH, levels in serum. Treatment with EB 24 h before or after a 500 micrograms dose of a GnRH antagonist did not reduce LH or FSH to levels lower than those achieved with antagonist alone. These results indicate that the GnRH-dependent component of FSH release and the GnRH-independent component that is unmasked in the presence of GnRH antagonist are sensitive to negative feedback by estrogen, indicating that this steroid is not the primary inhibitory ovarian factor regulating FSH in the rat.

Effects of melatonin on the production of GnRH and LH in luteal cells of pregnant sows

2021 ◽  
Author(s):  
Wenlong Zhang ◽  
Dewen Tong ◽  
Zelin Zhang ◽  
Jiang Peng ◽  
Sitian Yang ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Receptor Antagonist ◽  
Mrna Expression ◽  
Potential Role ◽  
Gonadotropin Releasing Hormone ◽  
Membrane Receptors ◽  
Corpora Lutea ◽  
Luteal Function ◽  
Luteal Cells ◽  
Lh Secretion

Effects of melatonin on the release and synthesis of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) at the hypothalamus and pituitary levels have been explored in some species, but a similar study in the corpora lutea (CL) has not yet been conducted. In this study, the immunostaining for GnRH and LH was observed in luteal cells of porcine CL during pregnancy, and a significant effect of pregnant stage on the level of GnRH and LH was found; higher values for GnRH and LH immunostaining and mRNA were detected in the early- and mid- stages CL than in the later-stage CL (P < 0.01). Furthermore, the patterns of melatonin membrane receptors (MT1 and MT2) expression were consistent with those of GnRH and LH expression in the CL of pregnant sows; the relative levels of MT1 and MT2 in the early- and mid- stages were significantly higher than those in the later-stage (P < 0.01). In luteal cells, melatonin dose-dependently increased in GnRH and LH secretion and mRNA expression. Melatonin also increased the GnRH–induced accumulation of LH, and the LH–induced secretion of P4 in luteal cells. Additionally, the effects of melatonin on luteal GnRH and LH production, were blocked by luzindole, a nonselective MT1 and MT2 receptor antagonist. Our results demonstrate the stimulatory effects of melatonin on GnRH and LH production in luteal cells of pregnant sows, suggesting a potential role for melatonin in luteal function through regulating the release and synthesis of GnRH and LH in luteal cells.

Dual intracellular pathways in gonadotropin releasing hormone (GnRH) induced desensitization of luteinizing hormone (LH) secretion

Life Sciences ◽  
1999 ◽  
Vol 64 (24) ◽  
pp. 2215-2223 ◽  
Author(s):  
M.Patricia Cassina ◽  
Lois C. Musgrove ◽  
L.Wayne Duck ◽  
Jeffrey C. Sellers ◽  
Jimmy D. Neill
Keyword(s):  
Luteinizing Hormone ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Intracellular Pathways ◽  
Lh Secretion
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