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

The functioning of the growth hormone (GH) and reproductive axis is known to be closely related: both GH overexpression and GH-deficiency are associated with dramatic decreases in fertility (Bartke, 1999; Bartke et al, 1999; 2002; Naar et al, 1991). Also, aging results in significant changes in functionality of both axes within a similar time frame. In the rat, GH secretion patterns are clearly sexually dimorphic (Clark et al, 1987; Eden et al, 1979; Gatford et al, 1998). This has been suggested to result mainly from differences in somatostatin (SOM) release patterns from the median eminence (ME) (Gillies, 1997; Muller et al, 1999; Tannenbaum et al, 1990). SOM is synthesized in the periventricular nucleus of the hypothalamus (PeVN) and controls in concert with GH-releasing hormone (GHRH) the GH release from the pituitary (Gillies, 1987; Tannenbaum et al, 1990; Terry and Martin, 1981; Zeitler et al, 1991). An altered GH status is reflected in changes in the hypothalamic SOM system. For instance, the number of SOM cells (Sasaki et al, 1997) and pre-pro SOM mRNA levels (Hurley and Phelps, 1992) in the PeVN were elevated in animals overexpressing GH. Several observations suggest that SOM may also affect reproductive function directly at the level of the hypothalamus. 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; 2003). Also, we previously showed that a single central injection with octreotide significantly attenuated the E2-induced Luteinizing Hormone (LH) surge and significantly decreased the activation of Gonadotropin Releasing Hormone (GnRH) cells in the hypothalamus of female rats (van Vugt et al, 2004). Age-related changes in fertility and fecundity are associated with selective changes at the level of the ovary and uterus (Meredith and Butcher, 1985; Nass et al, 1984; te Velde et al, 1998; Wise, 1982), pituitary gland (Brito et al, 1994; DePaolo et al, 1986; Krieg et al, 1995; Nass et al, 1984; Wise, 1982), and hypothalamus (Rubin et al, 1994; Wise, 1982; Wise et al, 2002). Reproductive aging is characterized by changes in the length of the reproductive