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

2. 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

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

4. 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
and Physiol review,2000

5. Corpus Luteum

6. 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

7. Progesterone – the structure

8. 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

9. 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

10. Biosynthesis of Ovarian steroids

11. Biosynthesis of P4

12. 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

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

14. 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

15. Neuroendocrine regulation – both pathways

16. 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

17. Short loop regulation

18. 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)

19. 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

20. P4 – mechanism of action

21. 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

22. 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

23. 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

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

25. 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
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

26. Low level/ Deficiency of P4
Deficiency of P4 is either due to :
low secretion from the corpus Luteum / placenta or:
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