Development of agonistic LHRH analogs

NestorJr., J. J.

doi:10.1007/978-94-009-5588-2_1

Cited by 16 publications

(2 citation statements)

References 23 publications

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“…It was forecast that chemical substitutions in the molecule would lead to analogues possessing antagonist or increased agonist activity, useful as anti-and profertility agents, respectively. Initial efforts were highly successful in generating highly potent agonist analogues: substitution of only one or two amino acids resulted in analogues with to 200 times the potency of the native molecule (4). However, the causes of this increase in potency, i.e.…”

Section: Introductionmentioning

confidence: 99%

GnRH and steroids in cancer

Florio¹

2002

Front Biosci

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Gonadotropin-releasing-hormone (GnRH) analogues are synthetic compounds derived from decapeptide neurohormones (LHRH; LH/FSH-RH). They have a key role in hormone dependent cancer, particularly breast and prostate cancer. GnRH analogues produce an efficient inhibition of gonadotropins and sex steroid hormones. Their use in cancer therapy result in a, pharmacological castration (i.e. ovariectomy and orchiectomy), providing an androgen and estrogen ablation. GnRH exert an inhibitory action on the growth of hormone-dependent human and canine mammary tumor. Mammary tumors can produce growth factor that potentially could modulate their own proliferation in an autocrine fashion (i.e. TGF-alpha and TGF-beta or with a paracrine mechanism (i.e. EGF, IGF, FGF). The expression of EGF receptors is related in mammary tissues to the action of oestrogen and progesteron and to the presence of functional receptors for oestrogen (ER) and progesteron (PR). The present review elucidate the role of GnRH receptors in cancer and their connection with steroid hormones. Besides we showed the link between GnRH and signal transductions pathways: Estrogen-receptors, GnRH-receptors, EGF-receptors signal transduction pathways. A very tight link exists between steroid hormones and GnRH analogues both on central pituitary gonadal axis and on tumor receptors peripherically. This last mechanism could be explained either locally activating GnRH receptors or locally interacting with EGF receptor-Intracellular NitricOxide system.

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Section: Introductionmentioning

confidence: 99%

GnRH and steroids in cancer

Florio¹

2002

Front Biosci

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“…5 Thus, GnRH analogues became available which were 200 times more potent than the natural decapeptide in stimulating the release of LH from the pituitary. 6 Since pituitary gonadotropins are essential for normal gonadal func-tions and hypothalamic GnRH was believed to act solely on the pituitary gland, the potent GnRH agonists were predicted to be a potential means for increasing fertility. However, early studies using the agonists (or long-term treatment with pharmacologic doses of the natural hormone) as ovulationinducing agents in anovulatory women were only partially successful.…”

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confidence: 99%