Effects of Polyamines on the Release of Gonadotropin-Releasing Hormone and Gonadotropins in Developing Female Rats

Abstract

Polyamines, putrescine (PUT), spermidine (SPD), spermine (SPM), and agmatine (AGM), are polycationic amines related to multiple cell functions found in high concentrations during the development of hypothalamus and pituitary. In previous works, we demonstrated that α-difluoromethylornithine (DFMO), an inhibitor of polyamines biosynthesis, induced a delay in puberty of female rats, accompanied by high, sustained follicle-stimulating hormone (FSH) levels during the infantile period. Also, DFMO treatment induced changes in polyamine concentration both in hypothalamus and pituitary of rats, mainly a decrease of PUT and SPD, an increase in SPM, and no change in AGM. In the present work, we investigated the direct effects of polyamines on the secretion of hypothalamic GnRH and pituitary gonadotropins in 6- and 15-day-old female rats. In 6-day-old animals, In vitro incubations with PUT, SPD, and AGM of hypothalami or anterior pituitaries were able to inhibit GnRH, FSH, and leutinlzing hormone (LH) secretion, respectively. SPM showed a nonspecific transient inhibitory effect on FSH. When challenged with either high K+ (hypothami) or GnRH (pituitaries), the tissues incubated in the presence of polyamines showed no differences when compared with their controls. No effects of polyamines in 15-day-old rats in either tissue were observed. Pituitary cell cultures of 6-day-old animals incubated with DFMO for 4 days showed a significant increase in FSH, but not in LH. We conclude that high PUT, SPD, and AGM levels during the first 10 days of life are important for the development of the hypothalamic-hypophyseal unit, probably related to an inhibitory effect on GnRH and gonadotropins. Therefore, polyamine participation, especially PUT and SPD, is of importance in the regulation of GnRH and gonadotropin secretion in the neonatal and infantile periods, critical stages in the establishment of sexual differentiation.

Regulation of the hypothalamic GnRH–GnIH system by putrescine in adult female rats and GT1‐7 neuronal cell line

“…A study identified polyamine as a regulator of GnRH‐I in 6‐ and 15‐day‐old female rats (Thyssen, Hockl, Chamson, Lux‐Lantos, & Carlos, 2002). This study further described through ex vivo approach that polyamine treatment to the hypothalamic and anterior pituitary tissue obtained from the 6‐ and 15‐ days old rats, regulated the secretion of GnRH‐I, FSH, and LH (Thyssen et al, 2002). Our group recently showed that polyamines and their associated factors had a positive correlation with the expression pattern of GnRH‐I in the medial preoptic area (MPA) during the estrous cycle of female rats (Fernandes et al, 2017).…”

“…This is the first report that shows that low dose putrescine treatment significantly (*** p < .001) increased the serum GnRH‐I levels, further increasing the serum gonadotropin levels. Thyssen et al (2002) previously showed that polyamines regulate FSH and LH using 6‐ and 15‐day‐old pituitary of female rats. Previous studies have shown that GnIH suppresses gonadotropin release by inhibiting GnRH‐I release (46,58).…”

“…| 223 4 | DISCUSSION GnRH-I secretion is stimulated by a variety of neurotransmitters and second messengers (de la Escalera, Choi, & Weiner, 1994;Moretto, Lopez, & Negro-Vilar, 1993;Yu et al, 1994) and there is a constant search for new GnRH-I regulators. A study identified polyamine as a regulator of GnRH-I in 6-and 15-day-old female rats (Thyssen, Hockl, Chamson, Lux-Lantos, & Carlos, 2002). This study further described through ex vivo approach that polyamine treatment to the hypothalamic and anterior pituitary tissue obtained from the 6-and 15-days old rats, regulated the secretion of GnRH-I, FSH, and LH (Thyssen et al, 2002).…”

Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

“…Liver levels of polyamines (putrescine, spermidine, and spermine) present in acid-extracts from cytosol were measured as benzoyl derivatives using HPLC (Beckman-Golden system HPLC with UV detector), prepared essentially as described by Thyssen et al [29]. The equipment used was a Beckman-Golden system HPLC with UV detector, and a C-18 reverse column was employed.…”

Differential gonadotropin releasing hormone (GnRH) expression, autoregulation and effects in two models of rat luteinized ovarian cells

“…GnRH concentration in culture media was determined as previously described (Thyssen et al, 2002). Briefly, samples were analyzed in duplicate using the anti GnRH antiserum (R1245 antiGnRH-BSA, final dilution 1 : 50,000) kindly provided by Dr Nett, GnRH was iodinated with 125 I (NEZ 03 3 H, DuPont NEN Life Sciences Products, Inc, Boston, MA) by the chloramin-T method.…”