Hormones of the ovary 2 - Progesterone Lecture NO: 2nd MBBS Dr Muhammad Ramzan

Progesterone (P4 - C21)- the definition Progesterone Is a steroid hormone secreted by the Corpus Luteum and the placenta – maintains the pregnancy Is regulated by the Pituitary Gonadotropins – FSH,LH Also called as P4/ Hormone of pregnancy

Progesterone – the background maintains pregnancy P4 acts to prepare the uterus for implantation of the fertilized ovum and maintains pregnancy 1 Promotes the development of the mammary glands 2 Regulates the monthly menstrual cycle 3 ↑ P4 is responsible for the Premenstrual Syndrome (PMS), 4 Breast tenderness, feeling bloated and mood swings. 5

Corpus Luteum (CL) Remains of Ovarian follicle CL, is a hormone secreting structure that develops in an ovary after an ovum has been discharged It degenerates after a few days unless pregnancy has been established – Changes into placenta. Primary function is the secretion of P4, but it also secrets moderate levels of Estradiol and Inhibin www.Radiopaediaa,org and Physiol review,2000

Corpus Luteum

Progesterone – the properties P4 is derived from Cholesterol in the SER of the Corpus Luteum and placental cells Is available both in free and bound form Progesterone is transported in binding with plasma Albumen or Steroid Binding Globulin

Progesterone – the structure

Progesterone – the Target tissues Target tissues are the ones with P4 receptors and include: All tissues of the female reproductive system Hepatic or liver cells Adipose tissues Renal tubular cells

Progesterone – the biosynthesis Steroid hormones are synthesized from Cholesterol (CH) which is abundantly present in the ovary CH is converted to Pregnenolone by the mitochondrial P450scc or Cholesterol Desmolase It is a rate limiting reaction – regulated by LH Pregnenolone is altered to Progestogens and further to Progesterone

Biosynthesis of Ovarian steroids

Biosynthesis of P4

Progesterone - Regulation of Secretion P4 is secreted by the Corpus Luteum after Ovulation/pregnancy Primary regulator is Luteinizing Hormone(LH) and is influenced by GnRH and GnIH If pregnancy occurs, placenta takes over the secretion after 2- 3 months

Regulation of P4 synthesis 2 pathways P4 is regulated through 2 pathways : Hypothalamic- Pituitary- Ovary axis or Neuroendocrine/ Long loop/indirect regulation 1 Short loop / Direct pathway – Pituitary- ovarian axis 2

Neuroendocrine / Long loop regulation It is the interaction B/W the circulating level of P4 and Hypothalamic - Pituitary – Ovary axis When P4 level is low, Hypothalamus is stimulated to secret GnRH that leads to secretion of Gonadotropins (FSH and LH) from the Pituitary Gonadotropins then stimulate the Corpus Luteum and Placenta to ↑the release of P4 Opposite is true when P4 level is high

Neuroendocrine regulation – both pathways

Direct / Short loop pathway It is the interaction B/w the circulating level of P4 and Gonadotropins from pituitary  in the circulating level of P4, inhibits the secretion of pituitary Gonadotropins and P4 from ovary Opposite is true when P4 is low

Short loop regulation

Progesterone - Mechanism of Action Is similar to the rest of the steroid hormones Both free as well as the bound forms cross the plasma membrane as they are Lipophilic P4 Binds with the Cytosolic Steroid Receptor forming the Hormone Receptor Complex -- HRC HRC is Translocated to the Nucleus at the acceptor site on the DNA strand - Hormone Response Element (HRE)

Progesterone- Mechanism of Action cont. The gene/HRE is activated and leads to the transcription of specific mRNA which get its exit from nucleus mRNA binds with Ribosome in the cytoplasm to translate new proteins and enzymes to: execute the hormone action

P4 – mechanism of action

Metabolic actions of Progesterone P4 is a key component in the regulation of normal female reproductive function These include actions on the female reproductive organs The Ovary, Uterus and mammary glands

Metabolic actions of P4 – the ovary and Uterus ↑P4 Releases mature oocytes and  the Basal Body Temperature by 0.5 C Facilitates the implantation of fertilized ovum in uterus Maintains the pregnancy by Uterine growth and suppression of Uterine contractility

Metabolic actions of P4 – uterus and mammary no action on bone cells Promotes the development and growth of glandular portion of the mammary gland for milk secretion after delivery P4 has no significant effect on bone Mediates the signals in brain for sexual response

Progesterone – Secretion abnormalities Progesterone may be secreted in excess or: there can be deficiency of Progesterone Both conditions give rise to important clinical conditions

Excess of P4 Elevated level of P4 is essential to implant the fertilized ovum in the uterus and maintains the pregnancy Promotes the uterine growth to accommodate the growing faetus throughout pregnancy Inhibits the uterine contraction till the child birth P4 is essential to maintain the pregnancy 1 Helps to Implant the fertilized ovum in the uterus, promotes its growth and development P4 Maintains the uterine growth through out pregnancy Inhibits the Uterine contractions

Low level/ Deficiency of P4 Deficiency of P4 is either due to : low secretion from the corpus Luteum / placenta or: 1 Non functioning P4 receptors due to genetic mutation Low P4 may results in abortion/miscarriage Low P4 level at the end of pregnancy, stimulates the uterine contractions for the delivery of the faetus