The effects of neurotransmitters and other cellular modulators and factors on hypothalamic and anterior pituitary Δ 4 -steroid (progesterone) 5α-reductase activity

• Published in: Steroids Vol. 36; no. 3; pp. 305 - 320
• Main Authors: Krause, James E., Halls, Juanita J., Karavolas, Harry J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.1980
• Subjects: 20-alpha-Dihydroprogesterone - analysis; 3-Hydroxysteroid Dehydrogenases - metabolism; Animals; Ascorbic Acid; Bacitracin - pharmacology; Dopamine - pharmacology; Edetic Acid; Female; Gonadotropin-Releasing Hormone - pharmacology; Hypothalamus - enzymology; Hypothalamus, Middle - enzymology; Neurotransmitter Agents - pharmacology; Pargyline - pharmacology; Pituitary Gland, Anterior - enzymology; Progesterone Reductase - metabolism; Rats; Serotonin - pharmacology; Serotonin Antagonists - pharmacology
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/0039-128X(80)90005-7

A number of diverse biological compounds involved in the regulation of the hypothalamo-hypophyseal-ovarian axis have been examined for effects on the conversion of 3H-progesterone to 3H-5α-dihydro-progesterone and 3H-3α-hydroxy-5α-pregnan-20-one by female rat hypothalamus and/or anterior pituitary. Broken cell preparations were incubated with 3H-progesterone and NADPH, and product 5α-reduced progestins were quantitated by reverse isotopic dilution analysis. Progesterone 5α-reductase activity was reduced up to 50% in the presence of 10 −2 to 10 −3 M serotonin in both preparations. At 10 −3 M, various indoles including n-acetylserotonin, melatonin, 5-methoxytryptamine, 5-methoxytryptophol, and 5-hydroxyindole acetic acid decreased by 10 to 30% 5α-reduced product formation. At 10 −2 M , carbamylcholine and norepinephrine were without effect, while 10 −2 M dopamine reduced by 20% the 5α-reduction of progesterone only in pituitary homogenates. The LHRH protease inhibitor bacitracin (2 × 10 −3 M ) decreased by 10 to 40% progesterone 5α-reductase activity in both tissues. By itself, LHRH did not affect the 5α-reduction of progesterone nor did it potentiate the bacitracin effect. In the presence of 1 n M ATP, 100 μ M cAMP and 100 μ M cGMP increased 5α-reduced product formation in the hypothalamus by 19 and 14%. The gonadotropins LH and FSH and the prostaglandins E 1, E 2, F 1α, and F 2α were without effect. Thus, these results and others indicate that a number of cellular components and other factors can affect the in vitro 5α-reduction of progesterone in broken cell preparations.