Variations in Hypothalamic Somatostatin Release and Content during the Estrous Cycle in the Rat

Abstract

To investigate the secretory pattern of somatostatin (SS) from the median eminence (ME) in the female rat, as well as estrogenic influence on this secretion, we measured both SS release and hypothalamic content in cycling, 10-day ovariectomized, and ovariectomized rats treated with estradiol for 3 days before. Animals were stereotaxically implanted with a push-pull cannula into the ME, and 10 days later the hypothalamic structure was perfused with artificial cerebrospinal fluid for 120–150 min at a regular flow rate of 17 µl/min. Secretion peaks were observed in the pattern of SS release, whatever the stage of the estrous cycle. The mean amplitude of SS peaks was similar throughout the cycle: 11.7 ± 4.0, 8.6 ± 1.5 and 10.5 ± 1.3 pg at proestrus, estrus and diestrus, respectively, and it was affected neither by ovariectomy (7.4 ± 1.3 pg) nor by estrogen replacement (5.5 ± 1.0 pg). By contrast, mean SS release levels in the proestrus phase were significantly higher than those measured in the other phases: 21.6 ± 2.1 vs. 17.7 ± 1.2 pg/15 min in diestrus (p < 0.05) and vs. 12.0 ± 0.7 pg/15 min in estrus (p < 0.001). Hypothalamic SS content showed variations quite similar to those observed during its release, i.e. with the highest values corresponding to the proestrus phase (1,170.5 ± 224.9 pg/mg of tissue) and to the diestrus (1,156.5 ± 332.1 pg/mg of tissue) and the lowest values in the estrus (511.5 ± 52.9 pg/mg of tissue; p < 0.05 vs. proestrus and diestrus). In addition, the lowest SS content and secretion values were found in ovariectomized animals: 95.5 ± 5.1 pg/mg of tissue (p < 0.001 compared to the values obtained for each stage of the estrous cycle) and 10.0 ± 0.9 pg/15 min (p < 0.001 vs. proestrus and diestrus), respectively. Patterns of SS release and SS hypothalamic content were not modified by estradiol treatment in ovariectomized animals. Our results suggest that (1) whatever the stage of the estrous cycle, SS release from the ME is not uniform and exhibits irregular peaks; (2) mean SS release levels were subjected to gonadal influence; (3) the occurrence of SS peaks seems to be estrogen-independent, and (4) variations in hypothalamic SS content were generally in good agreement with those of neurohormone release.

Somatostatin in the Periventricular Nucleus of the Female Rat: Age Specific Effects of Estrogen and Onset of Reproductive Aging

“…Estrogen did not affect total numbers of SOM-ir cells in the PeVN of young female rats in line with our previous studies (Van Vugt et al, 2008) and those of others (Estupina et al, 1996). Other studies reported a decrease in SOM mRNA content in the PeVN following OVX which was reversed by E 2 treatment Zorilla et al, 1991).…”

“…In the cycling female rat, elevated plasma concentrations of E 2 and P on the day of proestrus may increase NPY levels in the ARC that, together with the removed inhibitory GABA-ergic tone (Smith and Jennes, 2003), stimulate GnRH cell activation, leading to the GnRH surge and, subsequently, the preovulatory LH surge. Secondly, the increased levels of gonadal steroids (Estupina et al, 1996, Van Vugt et al, 2008, and in addition, elevated levels of NPY (Rettori et al, 1990) may increase SOM release from the ME. Elevated concentrations of SOM, in turn, inhibit either neuron activity in the OVLT/POA, or NPY and its stimulating effects on GnRH neurons, or both, leading to decreased GnRH cell activation and subsequently release, finally resulting in a decrease in plasma LH levels (see figure 2).…”

“…SOM synthesis in the hypothalamus and its release from the ME fluctuate over the estrous cycle. (Estupina et al, 1996, Zorrila et al, , 1991. Central injections with SOM or a SOM analog (octreotide) decreased the number of gonadotropic cells in the pituitary (Lovren et al, 1998;Nestorovic et al 2002;.…”

“…Evidence suggests that exposure to chronically elevated levels of circulating E 2 during life advances the decline in fertility with age (Lu et al, 1981;Rodrigues et al, 1993). Moreover, it is known that E 2 affects hypothalamic SOM content and release, although the literature is somewhat controversial on the precise role of E 2 on SOM cell function Estupina et al, 1996;Knuth et al, 1983;Murray et al, 1999;Werner et al, 1988;Zorilla et al, 1991). Recent studies demonstrated a clear sex difference in the number and distribution of SOM peptide containing cells in the PEVN.…”

Responsiveness to depolarization of hypothalamic neurons secreting somatostatin under stress and estrous cycle conditions: Involvement of GABAergic and steroidal interactions

“…The hypothalamic somatostatin neuron is a good model for studying these interactions, because of the following: 1) in male rats, somatostatin secretion is tonically inhibited by GABA because picrotoxin or bicuculline injections increase somatostatin release (Arancibia and Briozzo, 1990); 2) somatostatin release is modified in a number of stress responses (Arimura and Schally, 1976;Aguila et al, 1991;Benyassi et al, 1993), and its release is significantly decreased after cold exposure of rats, but this inhibition is blocked by prior injection of picrotoxin, a GABA-A receptor blocker ; 3) in female rats, hypothalamic somatostatin release is conspicuously influenced by physiological fluctuations of plasma estrogen-progesterone ratio (Estupina et al, 1996); 4) in vitro, in primary cultures of fetal hypothalamic neurons, GABA inhibits somatostatin release (Rage et al, 1992) and synthesis (Rage et al, 1994); and 5) in vitro, the neuroactive steroids allopregnanolone and allotetrahydroDOC selectively potentiate GABA inhibition of somatostatin release (Tapia- Arancibia et al, 1995).…”