scholarly journals Kisspeptin level in the aging ovary is regulated by the sympathetic nervous system

2017 ◽  
Vol 232 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Daniela Fernandois ◽  
Gonzalo Cruz ◽  
Eun Kyung Na ◽  
Hernán E Lara ◽  
Alfonso H Paredes

Previous work has demonstrated that the increase in the activity of sympathetic nerves, which occurs during the subfertility period in female rats, causes an increase in follicular cyst development and impairs follicular development. In addition, the increase in ovarian sympathetic activity of aged rats correlates with an increased expression of kisspeptin (KISS1) in the ovary. This increase in KISS1 could participate in the decrease in follicular development that occurs during the subfertility period. We aimed to determine whether the blockade of ovarian sympathetic tone prevents the increase in KISS1 expression during reproductive aging and improves follicular development. We performed 2 experiments in rats: (1) an in vivo blockade of beta-adrenergic receptor with propranolol (5.0 mg/kg) and (2) an ovarian surgical denervation to modulate the sympathetic system at these ages. We measured Kisspeptin and follicle-stimulating hormone receptor (FSHR) mRNA and protein levels by qRT-PCR and western blot and counted primordial, primary and secondary follicles at 8, 10 and 12 months of age. The results showed that ovarian KISS1 decreased but FSHR increased after both propranolol administration and the surgical denervation in rats of 8, 10 and 12 months of age. An increase in FSHR was related to an increase in the number of smaller secondary follicles and a decreased number of primordial follicles at 8, 10 and 12 months of age. These results suggest that intraovarian KISS1 is regulated by sympathetic nerves via a beta-adrenergic receptor and participates locally in ovarian follicular development in reproductive aging.

1989 ◽  
Vol 256 (3) ◽  
pp. E392-E400
Author(s):  
R. K. Studer ◽  
L. Ganas

The ontogeny of alpha 1- and beta-adrenergic receptors and their relative stimulation of phosphorylase alpha activity in hepatic tissue from male and female rats were compared. A decrease in beta-adrenergic receptor concentration and 4-(t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one HCl affinity for these sites was found in males and females, when data from membranes of 20- to 22-day animals was compared with that from neonates. No subsequent decline in receptor concentration was noted in the female; however, the beta-mediated phosphorylase activation was further diminished by 49-56 days, suggesting maturational changes beyond the receptor-adenylate cyclase system. Although high-affinity beta-adrenergic receptors were documented in membranes from pubertal males, they were not identified on the intact cells, and activation of phosphorylase alpha via the beta-pathway was minimal. This suggests the majority of the beta-receptors are sequestered in cellular sites not accessible to the hydrophilic ligand or epinephrine in the sexually mature male. Ontogeny of the alpha 1-adrenergic receptors was similar in males and females. Gonadectomy of mature males and females did not eliminate the sexual differences in adrenergic response. However, the ovariectomized females developed an enhanced basal and alpha-adrenergic stimulated phosphorylase activity. The rise in cytosolic free calcium in response to epinephrine was increased in the ovariectomized females to values seen in the intact male, whereas the response in the castrate male was depressed. The results suggest the dimorphism in alpha 1- and beta-adrenergic receptor function is determined by factors other than the ambient concentration of sex steroids in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)


2020 ◽  
Vol 244 (3) ◽  
pp. 523-533
Author(s):  
Miguel del Campo ◽  
Néstor Lagos ◽  
Hernán Lara

A high sympathetic tone is observed in the development and maintenance of the polycystic ovary (PCO) phenotype in rats. Neosaxitoxin (NeoSTX) specifically blocks neuronal voltage-dependent Na+ channels, and we studied the capacity of NeoSTX administered into the ovary to block sympathetic nerves and PCO phenotype that is induced by estradiol valerate (EV). The toxin was administered with a minipump inserted into the bursal cavity using two protocols: (1) the same day as EV administration and (2) 30 days after EV to block the final step of cyst development and maintenance of the condition. We studied the estrous cycling activity, follicular morphology, steroid plasma levels, and norepinephrine concentration. NeoSTX administered together with EV decreased NA intraovarian levels that were induced by EV, increased the number of corpora lutea, decreased the number of follicular cyst found after EV administration, and decreased the previously increased testosterone plasma levels induced by the PCO phenotype. Estrous cycling activity also recovered. NeoSTX applied after 30 days of EV administration showed near recovery of ovary function, suggesting that there is a specific window in which follicular development could be protected from cystic development. In addition, plasma testosterone levels decreased while those of progesterone increased. Our data strongly suggest that chronic inhibition of sympathetic nerves by a locally applied long-lasting toxin is a new tool to manage the polycystic phenotype in the rat and could be applied to other mammals depending on sympathetic nerve activity.


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